Structural and functional failure of fibrillin‑1 in human diseases (Review)

  • Authors:
    • Sandra Schrenk
    • Carola Cenzi
    • Thomas Bertalot
    • Maria Teresa Conconi
    • Rosa Di Liddo
  • View Affiliations

  • Published online on: December 22, 2017     https://doi.org/10.3892/ijmm.2017.3343
  • Pages: 1213-1223
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Abstract

Fibrillins (FBNs) are key relay molecules that form the backbone of microfibrils in elastic and non‑elastic tissues. Interacting with other components of the extracellular matrix (ECM), these ubiquitous glycoproteins exert pivotal roles in tissue development, homeostasis and repair. In addition to mechanical support, FBN networks also exhibit regulatory activities on growth factor signalling, ECM formation, cell behaviour and the immune response. Consequently, mutations affecting the structure, assembly and stability of FBN microfibrils have been associated with impaired biomechanical tissue properties, altered cell‑matrix interactions, uncontrolled growth factor or cytokine activation, and the development of fibrillinopathies and associated severe complications in multiple organs. Beyond a panoramic overview of structural cues of the FBN network, the present review will also describe the pathological implications of FBN disorders in the development of inflammatory and fibrotic conditions.

1. Introduction

Fibrillin (FBN)-1 is a calcium-binding protein that assembles to form 10–12 nm microfibrils in the extracellular matrix (ECM) of elastic and non-elastic tissues. The human gene FBN-1 spans >230 kb (1) on chromosome 15q15-21.1 (2) and is highly fragmented into 65 exons. The primary protein structure reveals multi-domains (3), which primarily consist of epidermal growth factor (EGF)-like and certain other modules (4). Out of a total of 47 EGF domains (5), 43 modules contain the calcium binding (cbEGF) consensus sequence D/N-XD/N-E/Q-Xm-D/N-Xn-Y/F (6), which provides structural stabilization (7), a characteristic rigid rod-like shape (810) and protection against proteolysis (11), and allows the control of self- or FBN-2-interaction (12,13) and interactions with ECM components, including fibulin-2, heparin/heparan sulphate and microfibril-associated glycoprotein (MAGP)-1 (1417). Disulphide bonds formed among the six cysteine residues in EGF and cbEGF, in a C1–C3, C2–C4 and C5–C6 pattern (9), contribute to further stabilize FBN-1. EGF-like domains are interspersed by seven transforming growth factor (TGF)-β binding protein (TB)-like modules and structurally related latent TGF-β-binding proteins (LTBPs) (18). Characterized by eight cysteine residues that form four disulphide bonds (C1–C3, C2–C6, C4–C7 and C5–C8 arrangement), TB domains occur seven times in FBN-1. Among them, the fourth TB module is of particular interest due to the presence of the cell binding site RGD (arginine-glycine-aspartic acid), which mediates interactions with integrins (19). Additionally, as with other FBNs, 'hybrid domains' are repeated twice in FBN-1 and are stabilized by four intradomain disulphide bonds in a C1–C3, C2–C5, C4–C6 and C7–C8 formation (20). The unique N- and C-terminal domains of FBN-1 include four and two cysteine residues, respectively, and contain the basic consensus sequence for processing by furin-type enzymes (2123). A distinguishing feature of FBN-1 is the presence of a proline-rich domain close to its N-terminus (4,24). A summary of the chromosomal location, domain organisation and primary functions of FBN-1 is presented in Fig. 1.

2. FBN network assembly and elastogenesis

FBN-1 is synthesized as an ~350 kDa precursor molecule, profibrillin-1, which requires proteolytic processing by furin proteases into its biologically active form (~320 kDa) prior to incorporation into microfibrils (22,25). Accounting for all microfibril structural features, FBN alignment models predict the initial interactions between the N- and C-terminal sequences, which cause a head-to-tail alignment and an approximate one-third stagger that is stable as a 56 nm folded form (2628). FBN bundles are stabilized by transglutaminase-derived cross-links (29). Microfibril assembly has been reported to be dependent and fine-tuned by a variety of FBN-associated proteins. When visualized by rotary electron microscopy (30), the extracted microfibrils exhibit a beaded string morphology with dark areas, which are termed 'bead' regions and appear in an average periodicity of 56 nm (31). Highlighting their important structural role, FBN microfibrils are essential for the process of elastogenesis, acting as a scaffold for the soluble precursor of elastin (tropoelastin) (32). Tropoelastin molecules are secreted and deposited extracellularly onto a preformed, organized FBN microfibril network, which gives rise to mature, elastic fibres that are subsequently processed by the lysyl oxidase enzyme for the formation of desmosine cross-links. The importance of FBN in the formation of elastic fibres is highlighted by the inability of FBN-1 knockout mice to form functioning elastic fibres, in addition to a disorganization of elastic fibres (33) and a reduction of tissue flexibility and extensibility, primarily in the arteries, lungs, skin and other dynamic connective tissues (17). Unlike cbEGF-cbEGF, EGF1-EGF2 and TB6-cbEGF32 are flexible domain interfaces (34,35).

3. Non-elastic components of the FBN network

FBN microfibrils interact with a large variety of ligands. The binding with ECM components involves the C-terminal regions of FBNs (36) and is essential for regulating protein assembly and functionality. Depending on the cell type, the FBN network (3639) and MAGP (4042) contribute to micro-fibril biogenesis. Additionally, fibulin-2 appears to colocalise with microfibrils in certain tissues at the interface between microfibrils and elastin (14). Fibulin-2 specifically binds to the N-terminal region of FBN-1, while it also interacts with fibronectin and exhibits a connecting role with other ECM molecules. As with fibulin-2, fibulin-1 localizes with elastin providing connective bridges to other ECM components and to cells through laminin, fibronectin, nidogen or fibrinogen (43). Contributing to elastic fibre assembly, fibulin-5 interacts with FBN and tropoelastin (44). According to experimental data, fibulin-5 null mice exhibit structural abnormalities due to disrupted elastogenesis (45,46). As they may be absent in tissues exerting strong tensional forces, such as tendons, fibulins are associated with elastic fibre assembly rather than the mechanical properties of microfibrils. Furthermore, studies have demonstrated that A disintegrin-like and metalloprotease (reprolysin-type) with thrombospondin type-1 motif (ADAMTS) and ADAMTS-like (ADAMTSL) proteins, including ADAMTSL4 (47), ADAMTSL6 (48) and ADAMTSL10 (49), bind to FBN and modulate microfibril assembly (49,50). If mutations occur in these genes, pathologies similar to fibrillinopathies are observed. Direct interaction of FBN with various proteoglycans are reported to be essential for network assembly and the maintenance of basement membranes (51,52). The proteoglycans decorin and biglycan are able to bind to tropoelastin, while only decorin directly interacts with FBN-1 (41,53). However, biglycan forms a ternary complex with tropoelastin and MAGP-1, indicating a potential role during elastogenesis (53). Notably, alterations in decorin expression have been observed in neonatal Marfan syndrome, which is connective tissue disorder (54,55). The heparan sulphate proteoglycan (HSPG) perlecan, also termed HSPG-2, colocalises with FBN and elastin (56), and binds to the central region of FBN-1 (57). Additionally, these HSPGs bind to cell surface molecules and growth factors (58), such as basic fibroblast growth factor, indicating an indirect involvement of FBN in the regulation of cell functions and stem cell niches (59,60). The chondroitin sulphate proteoglycan versican controls the genesis of elastic fibres (61,62) and acts as a key factor in inflammation by interacting with the adhesion molecules of activated leukocytes, including L-selectin, CD44 and chemokines, to recruit inflammatory cells (63,64). FBN-associated collagen with interrupted triple helices type XVI is associated with microfibrils in various tissues, including the upper papillary dermis (65) and dorsal root ganglia (66), indicating a potential association between FBN assembly and neuronal regeneration. LTBPs interact with FBN at the N-terminal region (16,67) while they are also anchored to other ECM components, such as fibronectin (6870). These interactions are important in regulating the availability and the activation of TGF-β deposited in the ECM. LTBP 1, 3 and 4 covalently bind to the small latent TGF-β complex with their third TB domain and control the local TGF-β bioavailability (71). In addition to TGF-β via LTBPs, a number of bone morphogenetic proteins (BMPs), and growth and differentiation factors, directly bind to FBN at the N-terminal region (7275). Furthermore, through the RGD binding site in the TB4 domain, FBN-1 interacts with different integrins that are responsible for cell-matrix communication.

4. FBN matrix: A dynamic deposit of growth factors

The FBN network is an important constituent of connective tissues that interacts with the cellular compartment. It controls the bioavailability and activity of the TGF-β superfamily, which activates specific cellular signalling pathways for preserving tissue homeostasis. The loss of cell matrix interactions is a factor implicated in the pathological manifestations observed in microfibrillinopathies (Fig. 2). By indirect interaction with FBN through LTBPs, as with TGF-β, or direct interaction, for example BMPs (76), growth factors regulate the cellular behaviour and control cell survival, differentiation and response to injury (77). TGF-β isoforms (TGF-β1, 2 and 3) are synthesized as precursor proteins that comprise a growth factor domain at the C-terminal end and a latency-associated peptide (LAP) at the N-terminus (78). Two precursor proteins homodimerize and, following cleavage by furin-like endoproteases, form a complex that is termed the small latent complex (SLC) (79), in which LAP is non-covalently bound to the active TGF-β dimer. The SLC binds covalently to the penultimate TB domain in LTBPs, which together form a complex termed the large latent complex (LLC). The C-terminal region of LTBP-1 and -4 exhibit non-covalent interactions with the N-terminus of FBN-1 within the core of beaded microfibrils, while the N-terminal regions bind to fibronectin. LTBP-3 localizes to microfibrils using a different mechanism (80). The LLC is biologically inactive and TGF-βs are accessible to its receptors following proteolytic degradation or conformational changes (81,82) induced by integrin binding or cell-mediated force transmission (79,83,84) The enzymatic activation followed by TGF-β release is reported to be mediated by matrix metalloprotease (MMP)-2 and -9 (85), the serine protease plasmin (8588), thrombospondin-1 (89) and reactive oxygen species (90). Following cleavage and activation, TGF-β binds to its serine and threonine kinase receptors (TβRI and TβRII) on cell membranes, forming a receptor heterocomplex (77,91) that, through Smad signalling activation (92,93), promotes the expression of target genes (94,95), including collagen type 1 α1 chain, collagen type 3 α1 chain and TIMP metallopeptidase inhibitor 1, in addition to another 60 ECM-associated genes (96). The direct binding of FBN-1 to different BMPs, including BMP-2, -4, -5, -7 and -10, has been previously reported (73,75,97). In addition, there is increasing evidence that other growth factors are indirectly controlled through targeting to other FBN binding partners within the ECM, such as perlecan (57).

5. Cellular sensing of FBN signalling

As reported by Zeyer and Reinhardt (80) in 2015, FBN-containing microfibrils, which contain one RGD binding site within the fourth TB domain (98), represent key signal relay molecules for cell attachment, gene expression, spreading, migration and proliferation. In vitro studies on cells cultured on FBN-1 RGD-containing peptides have established the impact of this interaction on cell adhesion and gene expression (99). Cellular interactions have been reported to be mediated via integrins (α5β1, α5β6, αvβ3, αvβ6 and α8β1) (19,99103) and, potentially, by other cellular sensors, including angiotensin II type 1 receptor (AT1) and proteoglycans, such as syndecans (35,104106). Mutations in regions close to the RGD binding site in FBN-1 lead to a condition that is termed stiff skin syndrome (SSS), a pathological condition that is characterized by excessive skin fibrosis and microfibril accumulation (107). In vitro and in vivo studies employing mice harbouring a mutation in this region reported disturbed cell contact with microfibrils and altered cell spreading. It is reported that AT1 is activated by mechanical stress in cardiac hypertrophy (108). Mice homozygous for a hypomorphic FBN-1 allele (FBN-1mgR/mgR) exhibited dilated cardiomyopathy (109). A heparin sulphate binding region upstream of the RGD motif has been reported to be synergistically involved in integrin binding, while another downstream heparan sulphate binding site stimulates the formation of focal adhesion (103) through αvβ3-integrin (110). It has been demonstrated that, when heparin sulphate signalling is inhibited, the formation of the FBN network is disrupted (104).

6. FBN diseases in humans

Due to the number of functions that are controlled to a certain degree by FBN, it is clear that mutations in FBN genes lead to a number of diseases that affect multiple organs, which are collectively termed fibrillinopathies. Mutations in the FBN-1 gene have been demonstrated to cause Marfan syndrome, an autosomal dominant disorder of the connective tissue that is characterized by pleiotropic manifestations in ocular, skeletal and cardiovascular systems. Since the identification of the first mutation in 1991 (111), at present, >1,800 genetic abnormalities have been identified throughout the entire length of FBN-1 (112). Unfortunately, due to phenotypic variability and disease severity, a phenotype-genotype correlation remains to be established (113,114). Mutations in the central region of the FBN-1 gene, comprising exons 24–32, are commonly associated with severe myocardial dysfunctions, neonatal Marfan syndrome and mortality within the first two years of postnatal life (115117). It is reported that approximately two-thirds of missense mutations involve cysteine residues and lead to ocular complications, while premature terminations are associated with severe skeletal and skin anomalies (115). A growing body of evidence indicates that not all mutations in FBN-1 result in Marfan syndrome; however, those that are not are associated with Marfan-like disorders (118), including MASS phenotype (119), familial thoracic aortic aneurysm (120,121), Shprintzen-Goldberg syndrome (122) and ectopia lentis (123). It has also been established that mutations in FBN-1 may lead to acromelic dysplasias, such as Weill-Marchesani syndrome (WMS), geleophysic dysplasia, acromicric dysplasia and Myhre syndrome (74,124,125). The patients affected by these syndromes generally exhibit short statue, short hands and feet, stiff joints and a hypermuscular build, which is unlike patients with Marfan syndrome, who present with a tall stature, arachnodactyly, hypermobile joints and a thin hypomuscular structure. By contrast to Marfan syndrome, the mutations in FBN-1 that cause acromelic dysplasias, such as WMS, are located in a hot spot within the FBN-1 gene (126) and are in-frame deletions of 24 nucleotides in exon 41 and 42, which encode the fifth TB (124,126,127). An in-frame deletion of exons 9–11, encoding the first TB domain, the proline rich region and the fourth EGF-like domain, have been identified in WMS (74). Notably, while FBN-1 mutations account for the dominant form of WMS, the recessive form is reported to be caused by mutations in ADAMTS10 (128). According to experimental evidence from mouse models expressing RGD sequence mutations and the ability of integrin-modulating therapy to prevent fibrosis and autoimmunity (129), the primary cause of SSS may be the loss of integrin binding sites. A mutation in the TB4 domain has also been reported in patients affected by this syndrome (107). A summary of the structural and signalling effects of mutations in FBN-1 is presented in Fig. 2.

7. In vitro and in vivo studies of FBN assembly

Pathophysiological mechanisms accounting for the clinical manifestation of Marfan syndrome and similar disorders are associated with an altered FBN network. Early immunofluo-rescent studies using anti-FBN antibodies revealed qualitative and quantitative abnormalities of the dermal microfibrils, with a fragmented appearance in tissues extracted from patients with Marfan syndrome. Isolated dermal fibroblasts exhibited a reduced expression of FBN fibres and an abnormal morphology in immunofluorescent analyses (130,131). Differences in microfibril morphology have also been observed in neonatal Marfan syndrome fibroblast cultures (132). In contrast to the fragmented FBN networks observed in Marfan syndrome (130,133), the FBN network in WMS is abnormal for a different reason, as large FBN aggregate accumulations (74) have been reported in the skin of patients with SSS (107). Several in vitro and in vivo studies of FBN-1 disorders have been performed in the last two decades. The dominant negative model is supported by an in vitro study in which the wild-type protein function is disrupted by the mutant FBN, indicating that one FBN-1 mutant allele is sufficient to diminish microfibril assembly (131). Furthermore, data from this model are consistent with published data that reported that low levels of mutant FBN-1 expression in patients with Marfan syndrome is associated with a less severe phenotype (134). On the other hand, haplosufficient models have demonstrated that selected mutations, such as C1039G, lead to a disorganization of the microfibril network, while the C1663R FBN-1 mutation participates in productive microfibril assembly (135). Based on this body of evidence, it is clear that FBN-1 disorders are caused by mechanisms that are dependent on the position and type of mutation. In vivo studies of mutant FBN have indicated that abnormalities within the first hybrid domain do not affect microfibril stability (133), while mutations in cbEGF-like domains perturb microfibril assembly (136). Certain FBN-1 mutations also lead to a gene product that, although it may be assembled into microfibrils with a normal appearance, the mutation destabilizes the structure of FBN-1 and renders it more susceptible to proteolysis, leading to a gradual degradation (137,138). As reported by several studies, the regulation of MMPs is implicated in the pathogenesis of Marfan syndrome and other fibrillinopathies (139,140). In particular, MMP-1, -2, -3 and -9 appear to exert a pivotal role in FBN fragmentation, as demonstrated by the increased concentration of FBN fragments in the aortic specimens of patients with Marfan syndrome (140142). Studies concerning connective tissue disorders caused by FBN-1 mutations have also revealed alterations in the targeting and activation of growth factors. In addition, an association between FBN-1 mutations and the altered release of TGF-β has been associated with the development of fibrillinopathies (143). In support of this hypothesis, the administration of TGF-β antagonists led to anti-apoptotic effects in the lungs of FBN-1-deficient mice (144). Additionally, neutralizing TGF-β antibodies successfully prevented the development of aortic aneurysm by normalizing the levels of TGF-β in Marfan syndrome mouse models (145). Furthermore, TGF-β antagonists have been reported to reduce the levels of circulating TGF-β in patients with Marfan syndrome (146). Notably, mutations in LTBPs or TGF-β receptors, as observed in Loyes-Dietz syndrome, may lead to the uncontrolled release of TGF-β. A perturbation of TGF-β signalling is also observed in other fibrillinopathies, including SSS (107) and acromicric or geleophysic dysplasia (124).

8. Involvement of FBN-1 in inflammatory disorders

Scleroderma is a heterogeneous connective tissue disease that is characterized by excessive cutaneous and visceral fibrosis, Raynaud's phenomenon, vascular lesions and gastrointestinal manifestations (147). A widely used mouse model of systemic sclerosis is the tight skin (Tsk) mouse, which exhibits an in-frame tandem duplication of FBN-1 (148). While homozygotes suffer embryonic lethality at day 7–8 of gestation, heterozygotes (Tsk/+) have a normal life span but manifest myocardial, skeletal, and pulmonary abnormalities. Furthermore, heterozygotes also present with abnormal/altered fibrotic, inflammatory and autoimmune function. Comparable levels of normal and mutant FBN-1 transcripts in Tsk/+ tissues, and the presence of abundant tissue microfibrils, indicates that the mutant FBN-1 is regularly synthesized and assembled (148). Mutant FBN copolymerizes with wild-type FBN-1, which leads to an unstable structure (149) that is more sensitive to proteolysis (150). Briefly, Tsk/+ mice synthesize two types of microfibrils that present with a normal morphology and a well-organized periodicity, or diffuse interbeads, a longer periodicity and a tendency to aggregate (151). The instability of Tsk microfibrils leads to a disorganization and fragmentation of elastic fibres, subsequently leading to reduced ECM integrity (152,153) and increased cellular processing, followed by an autoimmune response and the development of autoantibodies (154). The autoimmune phenotype, however, is not required for the development of dermal thickening observed in Tsk/+ mice, and the Tsk phenotype appears to be independent of the immune system, as this phenotype has also been reported in mice lacking mature T and B cells (155,156). A potential mechanism involved in the promotion of the fibrotic phenotype may be driven by altered TGF-β signalling (157).

9. Gut-FBN axis

Inflammatory bowel disease (IBD) comprises a group of gut immunopathological conditions that are a result of genetic, environmental and cellular cues (158). ECM components have important immunoregulatory roles, and the composition and ultrastructure of the ECM are involved in intestinal immune responses, pathological signalling, and chronic inflammation (159). Uncontrolled alterations in ECM composition are reported in IBD and involve collagen I (160), collagen III (161,162), collagen V (163), collagen XVI (164), laminin (165,166), hyaluronan (167) and, recently, FBN-1 (164). FBN and elastic fibre networks have important structural and biomechanical roles within the intestinal tract as they are essential for the peristaltic movement of the gastrointestinal tract. Notably, in up to 90% of patients with SSS (168), FBN network perturbations are reported to lead to excessive fibrosis, inflammation and vascular dysfunction (169175). Reinforcing the hypothesis that the FBN network is involved in intestinal homeostasis, a previous study reported the downregulation of FBN in the lamina propria of patients with IBD compared with healthy donors (164). The development of gut fibrosis (176) involves multiple cell types and a large number of soluble factors (Fig. 3). Among soluble factors, TGF-β1, which is generally considered to be the key mediator of fibrosis (177), is overexpressed in IBD (178), while under physiological conditions TGF-β1 regulates the immune homeostasis by preventing abnormal proinflammatory responses, as demonstrated by the development of severe and lethal systematic inflammation in TGF-β1 knockout mice (179) or animals expressing T cells that do not respond to TGF-β1 (180). As observed in other organs, FBN and elastin fragments deriving from unstable networks lead to the upregulated expression of MMPs, including MMP-1, -2, -3, -7, -9, -10, -12 and -13 (181183), which results in disturbed ECM turnover and subsequent fibrosis (184,185).

10. Conclusions and perspectives

FBN-1 is an important ECM component that integrates the biological network of structural and instructive information for the modulation of cell-cell and cell-matrix interactions. Acting as a key relay molecule for the transmission of extracellular information into cellular signalling and function, FBN-1 contributes to the accumulation of latent forms of growth factors, such as TGF-β and BMPs, and regulates their bioavailability and activity. Regulating the expression of MMPs, fragmented microfibrils are associated with the development of multiorgan inflammation and fibrosis. At present, the characterization of FBN-1 dysfunction has improved the characterization of the pathological pattern of connective tissue diseases and the identification of novel therapeutic biological approaches for the treatment of inflammation-associated states.

Acknowledgments

The present study was financially supported by a grant (PRID-2016, to Professor Rosa Di Liddo) from the University of Padova (Padova, Italy).

References

1 

Biery NJ, Eldadah ZA, Moore CS, Stetten G, Spencer F and Dietz HC: Revised genomic organization of FBN1 and significance for regulated gene expression. Genomics. 56:70–77. 1999. View Article : Google Scholar : PubMed/NCBI

2 

Kainulainen K, Pulkkinen L, Savolainen A, Kaitila I and Peltonen L: Location on chromosome 15 of the gene defect causing Marfan syndrome. N Engl J Med. 323:935–939. 1990. View Article : Google Scholar : PubMed/NCBI

3 

Robertson I, Jensen S and Handford P: TB domain proteins: Evolutionary insights into the multifaceted roles of fibrillins and LTBPs. Biochem J. 433:263–276. 2011. View Article : Google Scholar

4 

Corson GM, Chalberg SC, Dietz HC, Charbonneau NL and Sakai LY: Fibrillin binds calcium and is coded by cDNAs that reveal a multidomain structure and alternatively spliced exons at the 5′end. Genomics. 17:476–484. 1993. View Article : Google Scholar : PubMed/NCBI

5 

Maslen CL, Corson GM, Maddox BK, Glanville RW and Sakai LY: Partial sequence of a candidate gene for the Marfan syndrome. Nature. 352:334–337. 1991. View Article : Google Scholar : PubMed/NCBI

6 

Handford PA, Mayhew M and Brownlee GG: Calcium binding to fibrillin? Nature. 353:3951991. View Article : Google Scholar : PubMed/NCBI

7 

Werner JM, Knott V, Handford PA, Campbell ID and Downing AK: Backbone dynamics of a cbEGF domain pair in the presence of calcium. J Mol Biol. 296:1065–1078. 2000. View Article : Google Scholar : PubMed/NCBI

8 

Downing AK, Knott V, Werner JM, Cardy CM, Campbell ID and Handford PA: Solution structure of a pair of calcium-binding epidermal growth factor-like domains: Implications for the Marfan syndrome and other genetic disorders. Cell. 85:597–605. 1996. View Article : Google Scholar : PubMed/NCBI

9 

Smallridge RS, Whiteman P, Werner JM, Campbell ID, Handford PA and Downing AK: Solution structure and dynamics of a calcium binding epidermal growth factor-like domain pair from the neonatal region of human fibrillin-1. J Biol Chem. 278:12199–12206. 2003. View Article : Google Scholar : PubMed/NCBI

10 

Reinhardt DP, Mechling DE, Boswell BA, Keene DR, Sakai LY and Bächinger HP: Calcium determines the shape of fibrillin. J Biol Chem. 272:7368–7373. 1997. View Article : Google Scholar : PubMed/NCBI

11 

Reinhardt DP, Ono RN and Sakai LY: Calcium stabilizes fibrillin-1 against proteolytic degradation. J Biol Chem. 272:1231–1236. 1997. View Article : Google Scholar : PubMed/NCBI

12 

Lin G, Tiedemann K, Vollbrandt T, Peters H, Batge B, Brinckmann J and Reinhardt DP: Homo- and heterotypic fibrillin-1 and -2 interactions constitute the basis for the assembly of microfibrils. J Biol Chem. 277:50795–50804. 2002. View Article : Google Scholar : PubMed/NCBI

13 

Marson A, Rock MJ, Cain SA, Freeman LJ, Morgan A, Mellody K, Shuttleworth CA, Baldock C and Kielty CM: Homotypic fibrillin-1 interactions in microfibril assembly. J Biol Chem. 280:5013–5021. 2005. View Article : Google Scholar

14 

Reinhardt DP, Sasaki T, Dzamba BJ, Keene DR, Chu ML, Göhring W, Timpl R and Sakai LY: Fibrillin-1 and fibulin-2 interact and are colocalized in some tissues. J Biol Chem. 271:19489–19496. 1996. View Article : Google Scholar : PubMed/NCBI

15 

Jensen SA, Reinhardt DP, Gibson MA and Weiss AS: Protein interaction studies of MAGP-1 with tropoelastin and fibrillin-1. J Biol Chem. 276:39661–39666. 2001. View Article : Google Scholar : PubMed/NCBI

16 

Isogai Z, Ono RN, Ushiro S, Keene DR, Chen Y, Mazzieri R, Charbonneau NL, Reinhardt DP, Rifkin DB and Sakai LY: Latent transforming growth factor beta-binding protein 1 interacts with fibrillin and is a microfibril-associated protein. J Biol Chem. 278:2750–2757. 2003. View Article : Google Scholar

17 

Rock MJ, Cain SA, Freeman LJ, Morgan A, Mellody K, Marson A, Shuttleworth CA, Weiss AS and Kielty CM: Molecular basis of elastic fiber formation. Critical interactions and a tropoelastin-fibrillin-1 cross-link. J Biol Chem. 279:23748–23758. 2004. View Article : Google Scholar : PubMed/NCBI

18 

Robertson IB, Horiguchi M, Zilberberg L, Dabovic B, Hadjiolova K and Rifkin DB: Latent TGF-β-binding proteins. Matrix Biol. 47:44–53. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Jovanovic J, Takagi J, Choulier L, Abrescia NG, Stuart DI, van der Merwe PA, Mardon HJ and Handford PA: alphaVbeta6 is a novel receptor for human fibrillin-1. Comparative studies of molecular determinants underlying integrin-rgd affinity and specificity. J Biol Chem. 282:6743–6751. 2007. View Article : Google Scholar

20 

Jensen SA, Iqbal S, Lowe ED, Redfield C and Handford PA: Structure and interdomain interactions of a hybrid domain: A disulphide-rich module of the fibrillin/LTBP superfamily of matrix proteins. Structure. 17:759–768. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Lönnqvist L, Reinhardt D, Sakai L and Peltonen L: Evidence for furin-type activity-mediated C-terminal processing of profibrillin-1 and interference in the processing by certain mutations. Hum Mol Genet. 7:2039–2044. 1998. View Article : Google Scholar : PubMed/NCBI

22 

Raghunath M, Putnam EA, Ritty T, Hamstra D, Park ES, Tschödrich-Rotter M, Peters R, Rehemtulla A and Milewicz DM: Carboxy-terminal conversion of profibrillin to fibrillin at a basic site by PACE/furin-like activity required for incorporation in the matrix. J Cell Sci. 112:1093–1100. 1999.PubMed/NCBI

23 

Trask TM, Ritty TM, Broekelmann T, Tisdale C and Mecham RP: N-terminal domains of fibrillin 1 and fibrillin 2 direct the formation of homodimers: A possible first step in microfibril assembly. Biochem J. 340:693–701. 1999. View Article : Google Scholar : PubMed/NCBI

24 

Zhang H, Apfelroth SD, Hu W, Davis EC, Sanguineti C, Bonadio J, Mecham RP and Ramirez F: Structure and expression of fibrillin-2, a novel microfibrillar component preferentially located in elastic matrices. J Cell Biol. 124:855–863. 1994. View Article : Google Scholar : PubMed/NCBI

25 

Wallis DD, Putnam EA, Cretoiu JS, Carmical SG, Cao SN, Thomas G and Milewicz DM: Profibrillin-1 maturation by human dermal fibroblasts: Proteolytic processing and molecular chaperones. J Cell Biochem. 90:641–652. 2003. View Article : Google Scholar : PubMed/NCBI

26 

Reinhardt DP, Keene DR, Corson GM, Pöschl E, Bächinger HP, Gambee JE and Sakai LY: Fibrillin-1: Organization in microfibrils and structural properties. J Mol Biol. 258:104–116. 1996. View Article : Google Scholar : PubMed/NCBI

27 

Baldock C, Siegler V, Bax DV, Cain SA, Mellody KT, Marson A, Haston JL, Berry R, Wang MC, Grossmann JG, et al: Nanostructure of fibrillin-1 reveals compact conformation of EGF arrays and mechanism for extensibility. Proc Natl Acad Sci USA. 103:11922–11927. 2006. View Article : Google Scholar : PubMed/NCBI

28 

Kuo CL, Isogai Z, Keene DR, Hazeki N, Ono RN, Sengle G, Bächinger HP and Sakai LY: Effects of fibrillin-1 degradation on microfibril ultrastructure. J Biol Chem. 282:4007–4020. 2007. View Article : Google Scholar

29 

Qian RQ and Glanville RW: Alignment of fibrillin molecules in elastic microfibrils is defined by transglutaminase-derived cross-links. Biochemistry. 36:15841–15847. 1997. View Article : Google Scholar

30 

Keene DR, Maddox BK, Kuo HJ, Sakai LY and Glanville RW: Extraction of extendable beaded structures and their identification as fibrillin-containing extracellular matrix microfibrils. J Histochem Cytochem. 39:441–449. 1991. View Article : Google Scholar : PubMed/NCBI

31 

Kielty CM and Shuttleworth CA: Fibrillin-containing microfibrils: Structure and function in health and disease. Int J Biochem Cell Biol. 27:747–760. 1995. View Article : Google Scholar : PubMed/NCBI

32 

Kewley MA, Williams G and Steven FS: Studies of elastic tissue formation in the developing bovine ligamentum nuchae. J Pathol. 124:95–101. 1978. View Article : Google Scholar : PubMed/NCBI

33 

Carta L, Pereira L, Arteaga-Solis E, Lee-Arteaga SY, Lenart B, Starcher B, Merkel CA, Sukoyan M, Kerkis A, Hazeki N, et al: Fibrillins 1 and 2 perform partially overlapping functions during aortic development. J Biol Chem. 281:8016–8023. 2006. View Article : Google Scholar : PubMed/NCBI

34 

Yuan X, Werner JM, Lack J, Knott V, Handford PA, Campbell ID and Downing AK: Effects of the N2144S mutation on backbone dynamics of a TB-cbEGF domain pair from human fibrillin-1. J Mol Biol. 316:113–125. 2002. View Article : Google Scholar : PubMed/NCBI

35 

Yadin DA, Robertson IB, McNaught-Davis J, Evans P, Stoddart D, Handford PA, Jensen SA and Redfield C: Structure of the fibrillin-1 N-terminal domains suggests that heparan sulfate regulates the early stages of microfibril assembly. Structure. 21:1743–1756. 2013. View Article : Google Scholar : PubMed/NCBI

36 

Sabatier L, Chen D, Fagotto-Kaufmann C, Hubmacher D, McKee MD, Annis DS, Mosher DF and Reinhardt DP: Fibrillin assembly requires fibronectin. Mol Biol Cell. 20:846–858. 2008. View Article : Google Scholar : PubMed/NCBI

37 

Kinsey R, Williamson MR, Chaudhry S, Mellody KT, McGovern A, Takahashi S, Shuttleworth CA and Kielty CM: Fibrillin-1 microfibril deposition is dependent on fibronectin assembly. J Cell Sci. 121:2696–2704. 2008. View Article : Google Scholar : PubMed/NCBI

38 

Sabatier L, Djokic J, Fagotto-Kaufmann C, Chen M, Annis DS, Mosher DF and Reinhardt DP: Complex contributions of fibronectin to initiation and maturation of microfibrils. Biochem J. 456:283–295. 2013. View Article : Google Scholar : PubMed/NCBI

39 

Baldwin AK, Cain SA, Lennon R, Godwin A, Merry CL and Kielty CM: Epithelial-mesenchymal status influences how cells deposit fibrillin microfibrils. J Cell Sci. 127:158–171. 2014. View Article : Google Scholar :

40 

Gibson MA, Kumaratilake JS and Cleary EG: The protein components of the 12-nanometer microfibrils of elastic and nonelastic tissues. J Biol Chem. 264:4590–4598. 1989.PubMed/NCBI

41 

Trask BC, Trask TM, Broekelmann T and Mecham RP: The microfibrillar proteins MAGP-1 and fibrillin-1 form a ternary complex with the chondroitin sulfate proteoglycan decorin. Mol Biol Cell. 11:1499–1507. 2000. View Article : Google Scholar : PubMed/NCBI

42 

Mecham RP and Gibson MA: The microfibril-associated glycoproteins (MAGPs) and the microfibrillar niche. Matrix Biol. 47:13–33. 2015. View Article : Google Scholar : PubMed/NCBI

43 

Kostka G, Giltay R, Bloch W, Addicks K, Timpl R, Fässler R and Chu ML: Perinatal lethality and endothelial cell abnormalities in several vessel compartments of fibulin-1-deficient mice. Mol Cell Biol. 21:7025–7034. 2001. View Article : Google Scholar : PubMed/NCBI

44 

Freeman LJ, Lomas A, Hodson N, Sherratt MJ, Mellody KT, Weiss AS, Shuttleworth A and Kielty CM: Fibulin-5 interacts with fibrillin-1 molecules and microfibrils. Biochem J. 388:1–5. 2005. View Article : Google Scholar : PubMed/NCBI

45 

Yanagisawa H, Davis EC, Starcher BC, Ouchi T, Yanagisawa M, Richardson JA and Olson EN: Fibulin-5 is an elastin-binding protein essential for elastic fibre development in vivo. Nature. 415:168–171. 2002. View Article : Google Scholar : PubMed/NCBI

46 

Hirai M, Ohbayashi T, Horiguchi M, Okawa K, Hagiwara A, Chien KR, Kita T and Nakamura T: Fibulin-5/DANCE has an elastogenic organizer activity that is abrogated by proteolytic cleavage in vivo. J Cell Biol. 176:1061–1071. 2007. View Article : Google Scholar : PubMed/NCBI

47 

Gabriel LA, Wang LW, Bader H, Ho JC, Majors AK, Hollyfield JG, Traboulsi EI and Apte SS: ADAMTSL4, a secreted glycoprotein widely distributed in the eye, binds fibrillin-1 microfibrils and accelerates microfibril biogenesis. Invest Ophthalmol Vis Sci. 53:461–469. 2012. View Article : Google Scholar :

48 

Tsutsui K, Manabe R, Yamada T, Nakano I, Oguri Y, Keene DR, Sengle G, Sakai LY and Sekiguchi K: ADAMTSL-6 is a novel extracellular matrix protein that binds to fibrillin-1 and promotes fibrillin-1 fibril formation. J Biol Chem. 285:4870–4882. 2010. View Article : Google Scholar :

49 

Kutz WE, Wang LW, Bader HL, Majors AK, Iwata K, Traboulsi EI, Sakai LY, Keene DR and Apte SS: ADAMTS10 protein interacts with fibrillin-1 and promotes its deposition in extracellular matrix of cultured fibroblasts. J Biol Chem. 286:17156–17167. 2011. View Article : Google Scholar : PubMed/NCBI

50 

Hubmacher D and Apte SS: ADAMTS proteins as modulators of microfibril formation and function. Matrix Biol. 47:34–43. 2015. View Article : Google Scholar : PubMed/NCBI

51 

Iozzo RV: Basement membrane proteoglycans: From cellar to ceiling. Nat Rev Mol Cell Biol. 6:646–656. 2005. View Article : Google Scholar : PubMed/NCBI

52 

Murdoch AD, Liu B, Schwarting R, Tuan RS and Iozzo RV: Widespread expression of perlecan proteoglycan in basement membranes and extracellular matrices of human tissues as detected by a novel monoclonal antibody against domain III and by in situ hybridization. J Histochem Cytochem. 42:239–249. 1994. View Article : Google Scholar : PubMed/NCBI

53 

Reinboth B, Hanssen E, Cleary EG and Gibson MA: Molecular interactions of biglycan and decorin with elastic fiber components: Biglycan forms a ternary complex with tropoelastin and microfibril-associated glycoprotein 1. J Biol Chem. 277:3950–3957. 2002. View Article : Google Scholar

54 

Raghunath M, Superti-Furga A, Godfrey M and Steinmann B: Decreased extracellular deposition of fibrillin and decorin in neonatal Marfan syndrome fibroblasts. Hum Genet. 90:511–515. 1993. View Article : Google Scholar : PubMed/NCBI

55 

Superti-Furga A, Raghunath M and Willems PJ: Deficiencies of fibrillin and decorin in fibroblast cultures of a patient with neonatal Marfan syndrome. J Med Genet. 29:875–878. 1992. View Article : Google Scholar : PubMed/NCBI

56 

Hayes AJ, Lord MS, Smith SM, Smith MM, Whitelock JM, Weiss AS and Melrose J: Colocalization in vivo and association in vitro of perlecan and elastin. Histochem Cell Biol. 136:437–454. 2011. View Article : Google Scholar : PubMed/NCBI

57 

Tiedemann K, Sasaki T, Gustafsson E, Göhring W, Bätge B, Notbohm H, Timpl R, Wedel T, Schlötzer-Schrehardt U and Reinhardt DP: Microfibrils at basement membrane zones interact with perlecan via fibrillin-1. J Biol Chem. 280:11404–11412. 2005. View Article : Google Scholar : PubMed/NCBI

58 

Whitelock JM, Melrose J and Iozzo RV: Diverse cell signaling events modulated by perlecan. Biochemistry. 47:11174–11183. 2008. View Article : Google Scholar : PubMed/NCBI

59 

Kerever A, Mercier F, Nonaka R, de Vega S, Oda Y, Zalc B, Okada Y, Hattori N, Yamada Y and Arikawa-Hirasawa E: Perlecan is required for FGF-2 signaling in the neural stem cell niche. Stem Cell Res. 12:492–505. 2014. View Article : Google Scholar : PubMed/NCBI

60 

Thisse B and Thisse C: Functions and regulations of fibroblast growth factor signaling during embryonic development. Dev Biol. 287:390–402. 2005. View Article : Google Scholar : PubMed/NCBI

61 

Murasawa Y, Watanabe K, Yoneda M, Zako M, Kimata K, Sakai LY and Isogai Z: Homotypic versican G1 domain interactions enhance hyaluronan incorporation into fibrillin microfibrils. J Biol Chem. 288:29170–29181. 2013. View Article : Google Scholar : PubMed/NCBI

62 

Wight TN and Merrilees MJ: Proteoglycans in atherosclerosis and restenosis: Key roles for versican. Circ Res. 94:1158–1167. 2004. View Article : Google Scholar : PubMed/NCBI

63 

Wu YJ, La Pierre DP, Wu J, Yee AJ and Yang BB: The interaction of versican with its binding partners. Cell Res. 15:483–494. 2005. View Article : Google Scholar : PubMed/NCBI

64 

Zheng PS, Vais D, Lapierre D, Liang YY, Lee V, Yang BL and Yang BB: PG-M/versican binds to P-selectin glycoprotein ligand-1 and mediates leukocyte aggregation. J Cell Sci. 117:5887–5895. 2004. View Article : Google Scholar : PubMed/NCBI

65 

Grässel S, Unsöld C, Schäcke H, Bruckner-Tuderman L and Bruckner P: Collagen XVI is expressed by human dermal fibroblasts and keratinocytes and is associated with the microfibrillar apparatus in the upper papillary dermis. Matrix Biol. 18:309–317. 1999. View Article : Google Scholar : PubMed/NCBI

66 

Hubert T, Grimal S, Ratzinger S, Mechaly I, Grassel S and Fichard-Carroll A: Collagen XVI is a neural component of the developing and regenerating dorsal root ganglia extracellular matrix. Matrix Biol. 26:206–210. 2007. View Article : Google Scholar

67 

Ono RN, Sengle G, Charbonneau NL, Carlberg V, Bächinger HP, Sasaki T, Lee-Arteaga S, Zilberberg L, Rifkin DB, Ramirez F, et al: Latent transforming growth factor beta-binding proteins and fibulins compete for fibrillin-1 and exhibit exquisite specificities in binding sites. J Biol Chem. 284:16872–16881. 2009. View Article : Google Scholar : PubMed/NCBI

68 

Dallas SL, Sivakumar P, Jones CJ, Chen Q, Peters DM, Mosher DF, Humphries MJ and Kielty CM: Fibronectin regulates latent transforming growth factor-beta (TGF beta) by controlling matrix assembly of latent TGF-beta binding protein-1. J Biol Chem. 280:18871–18880. 2005. View Article : Google Scholar : PubMed/NCBI

69 

Fontana L, Chen Y, Prijatelj P, Sakai T, Fässler R, Sakai LY and Rifkin DB: Fibronectin is required for integrin alphavbeta6-mediated activation of latent TGF-beta complexes containing LTBP-1. FASEB J. 19:1798–1808. 2005. View Article : Google Scholar : PubMed/NCBI

70 

Kantola AK, Keski-Oja J and Koli K: Fibronectin and heparin binding domains of latent TGF-beta binding protein (LTBP)-4 mediate matrix targeting and cell adhesion. Exp Cell Res. 314:2488–2500. 2008. View Article : Google Scholar : PubMed/NCBI

71 

Saharinen J, Hyytiäinen M, Taipale J and Keski-Oja J: Latent transforming growth factor-beta binding proteins (LTBPs)-structural extracellular matrix proteins for targeting TGF-beta action. Cytokine Growth Factor Rev. 10:99–117. 1999. View Article : Google Scholar

72 

Gregory KE, Ono RN, Charbonneau NL, Kuo CL, Keene DR, Bachinger HP and Sakai LY: The prodomain of BMP-7 targets the BMP-7 complex to the extracellular matrix. J Biol Chem. 280:27970–27980. 2005. View Article : Google Scholar : PubMed/NCBI

73 

Sengle G, Charbonneau NL, Ono RN, Sasaki T, Alvarez J, Keene DR, Bächinger HP and Sakai LY: Targeting of bone morphogenetic protein growth factor complexes to fibrillin. J Biol Chem. 283:13874–13888. 2008. View Article : Google Scholar : PubMed/NCBI

74 

Sengle G, Tsutsui K, Keene DR, Tufa SF, Carlson EJ, Charbonneau NL, Ono RN, Sasaki T, Wirtz MK, Samples JR, et al: Microenvironmental regulation by fibrillin-1. PLoS Genet. 8:e10024252012. View Article : Google Scholar : PubMed/NCBI

75 

Wohl AP, Troilo H, Collins RF, Baldock C and Sengle G: Extracellular regulation of bone morphogenetic protein activity by the microfibril component fibrillin-1. J Biol Chem. 291:12732–12746. 2016. View Article : Google Scholar : PubMed/NCBI

76 

Charbonneau NL, Ono RN, Corson GM, Keene DR and Sakai LY: Fine tuning of growth factor signals depends on fibrillin microfibril networks. Birth Defects Res Part C Embryo Today. 72:37–50. 2004. View Article : Google Scholar

77 

Massagué J and Chen YG: Controlling TGF-beta signaling. Genes Dev. 14:627–644. 2000.PubMed/NCBI

78 

Lawrence DA, Pircher R, Krycève-Martinerie C and Jullien P: Normal embryo fibroblasts release transforming growth factors in a latent form. J Cell Physiol. 121:184–188. 1984. View Article : Google Scholar : PubMed/NCBI

79 

Shi M, Zhu J, Wang R, Chen X, Mi L, Walz T and Springer TA: Latent TGF-β structure and activation. Nature. 474:343–349. 2011. View Article : Google Scholar : PubMed/NCBI

80 

Zeyer KA and Reinhardt DP: Fibrillin-containing microfibrils are key signal relay stations for cell function. J Cell Commun Signal. 9:309–325. 2015. View Article : Google Scholar : PubMed/NCBI

81 

Dubois CM, Laprise MH, Blanchette F, Gentry LE and Leduc R: Processing of transforming growth factor beta 1 precursor by human furin convertase. J Biol Chem. 270:10618–10624. 1995. View Article : Google Scholar : PubMed/NCBI

82 

Nunes I, Munger J, Harpel JG, Nagano Y, Shapiro R, Gleizes PE and Rifkin DB: Structure and activation of the large latent transforming growth factor-Beta complex. J Am Optom Assoc. 69:643–648. 1998.PubMed/NCBI

83 

Annes JP, Munger JS and Rifkin DB: Making sense of latent TGFbeta activation. J Cell Sci. 116:217–224. 2003. View Article : Google Scholar

84 

Hinz B: It has to be the αv: Myofibroblast integrins activate latent TGF-β1. Nat Med. 19:1567–1568. 2013. View Article : Google Scholar : PubMed/NCBI

85 

Sato Y and Rifkin DB: Inhibition of endothelial cell movement by pericytes and smooth muscle cells: Activation of a latent transforming growth factor-beta 1-like molecule by plasmin during co-culture. J Cell Biol. 109:309–315. 1989. View Article : Google Scholar : PubMed/NCBI

86 

Yu Q and Stamenkovic I: Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. Genes Dev. 14:163–176. 2000.PubMed/NCBI

87 

Jenkins G: The role of proteases in transforming growth factor-beta activation. Int J Biochem Cell Biol. 40:1068–1078. 2008. View Article : Google Scholar : PubMed/NCBI

88 

Lyons RM, Gentry LE, Purchio AF and Moses HL: Mechanism of activation of latent recombinant transforming growth factor beta 1 by plasmin. J Cell Biol. 110:1361–1367. 1990. View Article : Google Scholar : PubMed/NCBI

89 

Schultz-Cherry S and Murphy-Ullrich JE: Thrombospondin causes activation of latent transforming growth factor-beta secreted by endothelial cells by a novel mechanism. J Cell Biol. 122:923–932. 1993. View Article : Google Scholar : PubMed/NCBI

90 

Barcellos-Hoff MH, Derynck R, Tsang ML and Weatherbee JA: Transforming growth factor-beta activation in irradiated murine mammary gland. J Clin Invest. 93:892–899. 1994. View Article : Google Scholar : PubMed/NCBI

91 

Schmierer B and Hill CS: TGFbeta-SMAD signal transduction: Molecular specificity and functional flexibility. Nat Rev Mol Cell Biol. 8:970–982. 2007. View Article : Google Scholar : PubMed/NCBI

92 

Chen X and Xu L: Mechanism and regulation of nucleocytoplasmic trafficking of smad. Cell Biosci. 1:402011. View Article : Google Scholar : PubMed/NCBI

93 

Tang LY and Zhang YE: Non-degradative ubiquitination in Smad-dependent TGF-β signaling. Cell Biosci. 1:432011. View Article : Google Scholar

94 

Feng XH and Derynck R: Specificity and versatility in tgf-beta signaling through Smads. Annu Rev Cell Dev Biol. 21:659–693. 2005. View Article : Google Scholar : PubMed/NCBI

95 

Massagué J, Seoane J and Wotton D: Smad transcription factors. Genes Dev. 19:2783–2810. 2005. View Article : Google Scholar : PubMed/NCBI

96 

Verrecchia F, Chu ML and Mauviel A: Identification of novel TGF-beta/Smad gene targets in dermal fibroblasts using a combined cDNA microarray/promoter transactivation approach. J Biol Chem. 276:17058–17062. 2001. View Article : Google Scholar : PubMed/NCBI

97 

Sengle G, Ono RN, Sasaki T and Sakai LY: Prodomains of transforming growth factor beta (TGFbeta) superfamily members specify different functions: Biglycan forms a ternary complex with tropoelastin and microfibril-associated glycoprotein 1. J Biol Chem. 286:5087–5099. 2011. View Article : Google Scholar

98 

Pereira L, D'Alessio M, Ramirez F, Lynch JR, Sykes B, Pangilinan T and Bonadio J: Genomic organization of the sequence coding for fibrillin, the defective gene product in Marfan syndrome. Hum Mol Genet. 2:17621993. View Article : Google Scholar : PubMed/NCBI

99 

Bax DV, Bernard SE, Lomas A, Morgan A, Humphries J, Shuttleworth CA, Humphries MJ and Kielty CM: Cell adhesion to fibrillin-1 molecules and microfibrils is mediated by alpha 5 beta 1 and alpha v beta 3 integrins. J Biol Chem. 278:34605–34616. 2003. View Article : Google Scholar : PubMed/NCBI

100 

Marek I, Volkert G, Hilgers KF, Bieritz B, Rascher W, Reinhardt DP and Hartner A: Fibrillin-1 and alpha8 integrin are co-expressed in the glomerulus and interact to convey adhesion of mesangial cells. Cell Adh Migr. 8:389–395. 2014. View Article : Google Scholar : PubMed/NCBI

101 

Lee SS, Knott V, Jovanović J, Harlos K, Grimes JM, Choulier L, Mardon HJ, Stuart DI and Handford PA: Structure of the integrin binding fragment from fibrillin-1 gives new insights into microfibril organization. Structure. 12:717–729. 2004. View Article : Google Scholar : PubMed/NCBI

102 

Bouzeghrane F, Reinhardt DP, Reudelhuber TL and Thibault G: Enhanced expression of fibrillin-1, a constituent of the myocardial extracellular matrix in fibrosis. Am J Physiol Heart Circ Physiol. 289:H982–H991. 2005. View Article : Google Scholar : PubMed/NCBI

103 

Bax DV, Mahalingam Y, Cain S, Mellody K, Freeman L, Younger K, Shuttleworth CA, Humphries MJ, Couchman JR and Kielty CM: Cell adhesion to fibrillin-1: Identification of an Arg-Gly-Asp-dependent synergy region and a heparin-binding site that regulates focal adhesion formation. J Cell Sci. 120:1383–1392. 2007. View Article : Google Scholar : PubMed/NCBI

104 

Tiedemann K, Bätge B, Müller PK and Reinhardt DP: Interactions of fibrillin-1 with heparin/heparan sulfate, implications for microfibrillar assembly. J Biol Chem. 276:36035–36042. 2001. View Article : Google Scholar : PubMed/NCBI

105 

Cain SA, Baldwin AK, Mahalingam Y, Raynal B, Jowitt TA, Shuttleworth CA, Couchman JR and Kielty CM: Heparan sulfate regulates fibrillin-1 N- and C-terminal interactions. J Biol Chem. 283:27017–27027. 2008. View Article : Google Scholar : PubMed/NCBI

106 

Alexopoulou AN, Multhaupt HA and Couchman JR: Syndecans in wound healing, inflammation and vascular biology. Int J Biochem Cell Biol. 39:505–528. 2007. View Article : Google Scholar

107 

Loeys BL, Gerber EE, Riegert-Johnson D, Iqbal S, Whiteman P, McConnell V, Chillakuri CR, Macaya D, Coucke PJ, De Paepe A, et al: Mutations in fibrillin-1 cause congenital scleroderma: Stiff skin syndrome. Sci Transl Med. 2:23ra202010. View Article : Google Scholar : PubMed/NCBI

108 

Zou Y, Akazawa H, Qin Y, Sano M, Takano H, Minamino T, Makita N, Iwanaga K, Zhu W, Kudoh S, et al: Mechanical stress activates angiotensin II type 1 receptor without the involvement of angiotensin II. Nat Cell Biol. 6:499–506. 2004. View Article : Google Scholar : PubMed/NCBI

109 

Cook JR, Carta L, Bénard L, Chemaly ER, Chiu E, Rao SK, Hampton TG, Yurchenco P; GenTAC Registry Consortium; Costa KD, et al: Abnormal muscle mechanosignaling triggers cardiomyopathy in mice with Marfan syndrome. J Clin Invest. 124:1329–1339. 2014.PubMed/NCBI

110 

Weber E, Rossi A, Solito R, Sacchi G, Agliano' M and Gerli R: Focal adhesion molecules expression and fibrillin deposition by lymphatic and blood vessel endothelial cells in culture. Microvasc Res. 64:47–55. 2002. View Article : Google Scholar : PubMed/NCBI

111 

Dietz HC, Cutting CR, Pyeritz RE, Maslen CL, Sakai LY, Corson GM, Puffenberger EG, Hamosh A, Nanthakumar EJ, Curristin SM, et al: Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature. 352:337–339. 1991. View Article : Google Scholar : PubMed/NCBI

112 

Collod-Béroud G, Le Bourdelles S, Ades L, Ala-Kokko L, Booms P, Boxer M, Child A, Comeglio P, De Paepe A, Hyland JC, et al: Update of the UMD-FBN1 mutation database and creation of an FBN1 polymorphism database. Hum Mutat. 22:199–208. 2003. View Article : Google Scholar : PubMed/NCBI

113 

Ramirez F and Dietz HC: Marfan syndrome: From molecular pathogenesis to clinical treatment. Curr Opin Genet Dev. 17:252–258. 2007. View Article : Google Scholar : PubMed/NCBI

114 

Sakai LY, Keene DR, Renard M and De Backer J: FBN1: The disease-causing gene for Marfan syndrome and other genetic disorders. Gene. 591:279–291. 2016. View Article : Google Scholar : PubMed/NCBI

115 

Faivre L, Collod-Beroud G, Loeys BL, Child A, Binquet C, Gautier E, Callewaert B, Arbustini E, Mayer K, Arslan-Kirchner M, et al: Effect of mutation type and location on clinical outcome in 1,013 probands with marfan syndrome or related phenotypes and fbn1 mutations: An international study. Am J Hum Genet. 81:454–466. 2007. View Article : Google Scholar : PubMed/NCBI

116 

Booms P, Cisler J, Mathews KR, Godfrey M, Tiecke F, Kaufmann UC, Vetter U, Hagemeier C and Robinson PN: Novel exon skipping mutation in the fibrillin-1 gene: Two 'hot spots' for the neonatal Marfan syndrome. Clin Genet. 55:110–117. 1999. View Article : Google Scholar : PubMed/NCBI

117 

Morse RP, Rockenmacher S, Pyeritz RE, Sanders SP, Bieber FR, Lin A, MacLeod P, Hall B and Graham JM Jr: Diagnosis and management of infantile marfan syndrome. Pediatrics. 86:888–895. 1990.PubMed/NCBI

118 

Loeys BL, Dietz HC, Braverman AC, Callewaert BL, De Backer J, Devereux RB, Hilhorst-Hofstee Y, Jondeau G, Faivre L, Milewicz DM, et al: The revised Ghent nosology for the Marfan syndrome. J Med Genet. 47:476–485. 2010. View Article : Google Scholar : PubMed/NCBI

119 

Dietz HC and Pyeritz RE: Mutations in the human gene for fibrillin-1 (FBN1) in the Marfan syndrome and related disorders. Hum Mol Genet. 4(Spec No): 1799–1809. 1995. View Article : Google Scholar : PubMed/NCBI

120 

Francke U, Berg MA, Tynan K, Brenn T, Liu W, Aoyama T, Gasner C, Miller DC and Furthmayr H: A Gly1127Ser mutation in an EGF-like domain of the fibrillin-1 gene is a risk factor for ascending aortic aneurysm and dissection. Am J Hum Genet. 56:1287–1296. 1995.PubMed/NCBI

121 

Yamawaki T, Nagaoka K, Morishige K, Sadamatsu K, Tashiro H, Yasunaga H, Morisaki H and Morisaki T: Familial thoracic aortic aneurysm and dissection associated with Marfan-related gene mutations: Case report of a family with two gene mutations. Intern Med. 48:555–558. 2009. View Article : Google Scholar : PubMed/NCBI

122 

Sood S, Eldadah ZA, Krause WL, McIntosh I and Dietz HC: Mutation in fibrillin-1 and the Marfanoid-craniosynostosis (Shprintzen-Goldberg) syndrome. Nat Genet. 12:209–211. 1996. View Article : Google Scholar : PubMed/NCBI

123 

Kainulainen K, Karttunen L, Puhakka L, Sakai L and Peltonen L: Mutations in the fibrillin gene responsible for dominant ectopia lentis and neonatal Marfan syndrome. Nat Genet. 6:64–69. 1994. View Article : Google Scholar : PubMed/NCBI

124 

Le Goff C, Mahaut C, Wang LW, Allali S, Abhyankar A, Jensen S, Zylberberg L, Collod-Beroud G, Bonnet D, Alanay Y, et al: Mutations in the TGFβ Binding-protein-like domain 5 of FBN1 are responsible for acromicric and geleophysic dysplasias. Am J Hum Genet. 89:7–14. 2011. View Article : Google Scholar : PubMed/NCBI

125 

Faivre L, Dollfus H, Lyonnet S, Alembik Y, Mégarbané A, Samples J, Gorlin RJ, Alswaid A, Feingold J, Le Merrer M, et al: Clinical homogeneity and genetic heterogeneity in Weill-Marchesani syndrome. Am J Med Genet A. 123A:204–207. 2003. View Article : Google Scholar : PubMed/NCBI

126 

Cecchi A, Ogawa N, Martinez HR, Carlson A, Fan Y, Penny DJ, Guo DC, Eisenberg S, Safi H, Estrera A, et al: Missense mutations in FBN1 exons 41 and 42 cause Weill-Marchesani syndrome with thoracic aortic disease and Marfan syndrome. Am J Med Genet Part A. 161A:2305–2310. 2013. View Article : Google Scholar : PubMed/NCBI

127 

Faivre L, Gorlin RJ, Wirtz MK, Godfrey M, Dagoneau N, Samples JR, Le Merrer M, Collod-Beroud G, Boileau C, Munnich A and Cormier-Daire V: In frame fibrillin-1 gene deletion in autosomal dominant Weill-Marchesani syndrome. J Med Genet. 40:34–36. 2003. View Article : Google Scholar : PubMed/NCBI

128 

Dagoneau N, Benoist-Lasselin C, Huber C, Faivre L, Mégarbané A, Alswaid A, Dollfus H, Alembik Y, Munnich A, Legeai-Mallet L and Cormier-Daire V: ADAMTS10 mutations in autosomal recessive Weill-Marchesani syndrome. Am J Hum Genet. 75:801–806. 2004. View Article : Google Scholar : PubMed/NCBI

129 

Gerber EE, Gallo EM, Fontana SC, Davis EC, Wigley FM, Huso DL and Dietz HC: Integrin-modulating therapy prevents fibrosis and autoimmunity in mouse models of scleroderma. Nature. 503:126–130. 2013. View Article : Google Scholar : PubMed/NCBI

130 

Hollister DW, Godfrey M, Sakai LY and Pyeritz RE: Immunohistologic abnormalities of the Microfibrillar-fiber system in the marfan syndrome. N Engl J Med. 323:152–159. 1990. View Article : Google Scholar : PubMed/NCBI

131 

Eldadah ZA, Brenn T, Furthmayr H and Dietz HC: Expression of a mutant human fibrillin allele upon a normal human or murine genetic background recapitulates a Marfan cellular phenotype. J Clin Invest. 95:874–880. 1995. View Article : Google Scholar : PubMed/NCBI

132 

Godfrey M, Raghunath M, Cisler J, Bevins CL, DePaepe A, Di Rocco M, Gregoritch J, Imaizumi K, Kaplan P, Kuroki Y, et al: Abnormal morphology of fibrillin microfibrils in fibroblast cultures from patients with neonatal Marfan syndrome. Am J Pathol. 146:1414–1421. 1995.PubMed/NCBI

133 

Charbonneau NL, Carlson EJ, Tufa S, Sengle G, Manalo EC, Carlberg VM, Ramirez F, Keene DR and Sakai LY: In vivo studies of mutant Fibrillin-1 microfibrils. J Biol Chem. 285:24943–24955. 2010. View Article : Google Scholar : PubMed/NCBI

134 

Aoyama T, Tynan K, Dietz HC, Francke U and Furthmayr H: Missense mutations impair intracellular processing of fibrillin and microfibril assembly in Marfan syndrome. Hum Mol Genet. 2:2135–2140. 1993. View Article : Google Scholar : PubMed/NCBI

135 

Judge DP, Biery NJ, Keene DR, Geubtner J, Myers L, Huso DL, Sakai LY and Dietz HC: Evidence for a critical contribution of haploinsufficiency in the complex pathogenesis of Marfan syndrome. J Clin Invest. 114:172–181. 2004. View Article : Google Scholar : PubMed/NCBI

136 

Arbustini E, Grasso M, Ansaldi S, Malattia C, Pilotto A, Porcu E, Disabella E, Marziliano N, Pisani A, Lanzarini L, et al: Identification of sixty-two novel and twelve known FBN1 mutations in eighty-one unrelated probands with Marfan syndrome and other fibrillinopathies. Hum Mutat. 26:4942005. View Article : Google Scholar : PubMed/NCBI

137 

Reinhardt DP, Ono RN, Notbohm H, Müller PK, Bächinger HP and Sakai LY: Mutations in calcium-binding epidermal growth factor modules render fibrillin-1 susceptible to proteolysis. A potential disease-causing mechanism in Marfan syndrome. J Biol Chem. 275:12339–12345. 2000. View Article : Google Scholar : PubMed/NCBI

138 

Booms P, Tiecke F, Rosenberg T, Hagemeier C and Robinson PN: Differential effect of FBN1 mutations on in vitro proteolysis of recombinant fibrillin-1 fragments. Hum Genet. 107:216–224. 2000. View Article : Google Scholar : PubMed/NCBI

139 

Hindson VJ, Ashworth JL, Rock MJ, Cunliffe S, Shuttleworth CA and Kielty CM: Fibrillin degradation by matrix metalloproteinases: Identification of amino- and carboxy-terminal cleavage sites. FEBS Lett. 452:195–198. 1999. View Article : Google Scholar : PubMed/NCBI

140 

Ikonomidis JS, Jones JA, Barbour JR, Stroud RE, Clark LL, Kaplan BS, Zeeshan A, Bavaria JE, Gorman JH III, Spinale FG and Gorman RC: Expression of matrix metalloproteinases and endogenous inhibitors within ascending aortic aneurysms of patients with Marfan syndrome. Circulation. 114(Suppl 1): I365–I370. 2006. View Article : Google Scholar : PubMed/NCBI

141 

Segura AM, Luna RE, Horiba K, Stetler-Stevenson WG, McAllister HA Jr, Willerson JT and Ferrans VJ: Immunohistochemistry of matrix metalloproteinases and their inhibitors in thoracic aortic aneurysms and aortic valves of patients with Marfan's syndrome. Circulation. 98(Suppl 19): II331–II338. 1998.PubMed/NCBI

142 

Fleischer KJ, Nousari HC, Anhalt GJ, Stone CD and Laschinger JC: Immunohistochemical abnormalities of fibrillin in cardiovascular tissues in Marfan's syndrome. Ann Thorac Surg. 63:1012–1017. 1997. View Article : Google Scholar : PubMed/NCBI

143 

Granata A, Serrano F, Bernard WG, McNamara M, Low L, Sastry P and Sinha S: An iPSC-derived vascular model of Marfan syndrome identifies key mediators of smooth muscle cell death. Nat Genet. 49:97–109. 2017. View Article : Google Scholar

144 

Neptune ER, Frischmeyer PA, Arking DE, Myers L, Bunton TE, Gayraud B, Ramirez F, Sakai LY and Dietz HC: Dysregulation of TGF-beta activation contributes to pathogenesis in Marfan syndrome. Nat Genet. 33:407–411. 2003. View Article : Google Scholar : PubMed/NCBI

145 

Ng CM, Cheng A, Myers LA, Martinez-Murillo F, Jie C, Bedja D, Gabrielson KL, Hausladen JM, Mecham RP, Judge DP and Dietz HC: TGF-beta-dependent pathogenesis of mitral valve prolapse in a mouse model of Marfan syndrome. J Clin Invest. 114:1586–1592. 2004. View Article : Google Scholar : PubMed/NCBI

146 

Franken R, den Hartog AW, de Waard V, Engele L, Radonic T, Lutter R, Timmermans J, Scholte AJ, van den Berg MP, Zwinderman AH, et al: Circulating transforming growth factor-β as a prognostic biomarker in Marfan syndrome. Int J Cardiol. 168:2441–2446. 2013. View Article : Google Scholar : PubMed/NCBI

147 

Pattanaik D, Brown M and Postlethwaite AE: Vascular involvement in systemic sclerosis (scleroderma). J Inflamm Res. 4:105–125. 2011.PubMed/NCBI

148 

Siracusa LD, McGrath R, Ma Q, Moskow JJ, Manne J, Christner PJ, Buchberg AM and Jimenez SA: A tandem duplication within the fibrillin 1 gene is associated with the mouse tight skin mutation. Genome Res. 6:300–313. 1996. View Article : Google Scholar : PubMed/NCBI

149 

Lemaire R, Bayle J and Lafyatis R: Fibrillin in Marfan syndrome and tight skin mice provides new insights into transforming growth factor-beta regulation and systemic sclerosis. Curr Opin Rheumatol. 18:582–587. 2006. View Article : Google Scholar : PubMed/NCBI

150 

Gayraud B, Keene DR, Sakai LY and Ramirez F: New insights into the assembly of extracellular microfibrils from the analysis of the fibrillin 1 mutation in the tight skin mouse. J Cell Biol. 150:667–680. 2000. View Article : Google Scholar : PubMed/NCBI

151 

Kielty CM, Raghunath M, Siracusa LD, Sherratt MJ, Peters R, Shuttleworth CA and Jimenez SA: The tight skin mouse: Demonstration of mutant fibrillin-1 production and assembly into abnormal microfibrils. J Cell Biol. 140:1159–1166. 1998. View Article : Google Scholar : PubMed/NCBI

152 

Saito S, Nishimura H, Brumeanu TD, Casares S, Stan AC, Honjo T and Bona CA: Characterization of mutated protein encoded by partially duplicated fibrillin-1 gene in tight skin (TSK) mice. Mol Immunol. 36:169–176. 1999. View Article : Google Scholar : PubMed/NCBI

153 

Gardi C, Martorana PA, de Santi MM, van Even P and Lungarella G: A biochemical and morphological investigation of the early development of genetic emphysema in tight-skin mice. Exp Mol Pathol. 50:398–410. 1989. View Article : Google Scholar : PubMed/NCBI

154 

Tan FK, Arnett FC, Antohi S, Saito S, Mirarchi A, Spiera H, Sasaki T, Shoichi O, Takeuchi K, Pandey JP, et al: Autoantibodies to the extracellular matrix microfibrillar protein, fibrillin-1, in patients with scleroderma and other connective tissue diseases. J Immunol. 163:1066–1072. 1999.PubMed/NCBI

155 

Siracusa LD, McGrath R, Fisher JK and Jimenez SA: The mouse tight skin (Tsk) phenotype is not dependent on the presence of mature T and B lymphocytes. Mamm Genome. 9:907–909. 1998. View Article : Google Scholar : PubMed/NCBI

156 

Dodig TD, Mack KT, Cassarino DF and Clark SH: Development of the tight-skin phenotype in immune-deficient mice. Arthritis Rheum. 44:723–727. 2001. View Article : Google Scholar : PubMed/NCBI

157 

Kissin EY, Lemaire R, Korn JH and Lafyatis R: Transforming growth factor beta induces fibroblast fibrillin-1 matrix formation. Arthritis Rheum. 46:3000–3009. 2002. View Article : Google Scholar : PubMed/NCBI

158 

Podolsky DK: Inflammatory bowel disease. N Engl J Med. 347:417–429. 2002. View Article : Google Scholar : PubMed/NCBI

159 

Shimshoni E, Yablecovitch D, Baram L, Dotan I and Sagi I: ECM remodelling in IBD: Innocent bystander or partner in crime? The emerging role of extracellular molecular events in sustaining intestinal inflammation. Gut. 64:367–372. 2015. View Article : Google Scholar :

160 

Stumpf M, Cao W, Klinge U, Klosterhalfen B, Junge K, Krones CJ and Schumpelick V: Reduced expression of collagen type I and increased expression of matrix metalloproteinases 1 in patients with Crohn's disease. J Invest Surg. 18:33–38. 2005. View Article : Google Scholar : PubMed/NCBI

161 

Stumpf M, Cao W, Klinge U, Klosterhalfen B, Kasperk R and Schumpelick V: Increased distribution of collagen type III and reduced expression of matrix metalloproteinase 1 in patients with diverticular disease. Int J Colorectal Dis. 16:271–275. 2001. View Article : Google Scholar : PubMed/NCBI

162 

Stallmach A, Schuppan D, Riese HH, Matthes H and Riecken EO: Increased collagen type III synthesis by fibroblasts isolated from strictures of patients with Crohn's disease. Gastroenterology. 102:1920–1929. 1992. View Article : Google Scholar : PubMed/NCBI

163 

Graham MF, Diegelmann RF, Elson CO, Lindblad WJ, Gotschalk N, Gay S and Gay R: Collagen content and types in the intestinal strictures of Crohn's disease. Gastroenterology. 94:257–265. 1988. View Article : Google Scholar : PubMed/NCBI

164 

Ratzinger S, Eble JA, Pasoldt A, Opolka A, Rogler G, Grifka J and Grässel S: Collagen XVI induces formation of focal contacts on intestinal myofibroblasts isolated from the normal and inflamed intestinal tract. Matrix Biol. 29:177–193. 2010. View Article : Google Scholar

165 

Koutroubakis IE, Petinaki E, Dimoulios P, Vardas E, Roussomoustakaki M, Maniatis AN and Kouroumalis EA: Serum laminin and collagen IV in inflammatory bowel disease. J Clin Pathol. 56:817–820. 2003. View Article : Google Scholar : PubMed/NCBI

166 

Spenlé C, Lefebvre O, Lacroute J, Méchine-Neuville A, Barreau F, Blottière HM, Duclos B, Arnold C, Hussenet T, Hemmerlé J, et al: The laminin response in inflammatory bowel disease: Protection or malignancy? PLoS One. 9:e1113362014. View Article : Google Scholar : PubMed/NCBI

167 

de la Motte CA: Hyaluronan in intestinal homeostasis and inflammation: Implications for fibrosis. Am J Physiol Gastrointest Liver Physiol. 301:G945–G949. 2011. View Article : Google Scholar : PubMed/NCBI

168 

Sallam H, McNearney TA and Chen JD: Systematic review: Pathophysiology and management of gastrointestinal dysmotility in systemic sclerosis (scleroderma). Aliment Pharmacol Ther. 23:691–712. 2006. View Article : Google Scholar : PubMed/NCBI

169 

Sjogren RW: Gastrointestinal motility disorders in scleroderma. Arthritis Rheum. 37:1265–1282. 1994. View Article : Google Scholar : PubMed/NCBI

170 

Marie I, Ducrotté P, Denis P, Hellot MF and Levesque H: Outcome of small-bowel motor impairment in systemic sclerosis-a prospective manometric 5-yr follow-up. Rheumatology (Oxford). 46:150–153. 2007. View Article : Google Scholar

171 

Greydanus MP and Camilleri M: Abnormal postcibal antral and small bowel motility due to neuropathy or myopathy in systemic sclerosis. Gastroenterology. 96:110–115. 1989. View Article : Google Scholar : PubMed/NCBI

172 

Iovino P, Valentini G, Ciacci C, De Luca A, Tremolaterra F, Sabbatini F, Tirri E and Mazzacca G: Proximal stomach function in systemic sclerosis: Relationship with autonomic nerve function. Dig Dis Sci. 46:723–730. 2001. View Article : Google Scholar : PubMed/NCBI

173 

Ibba-Manneschi L, Del Rosso A, Pacini S, Tani A, Bechi P and Matucci Cerinic M: Ultrastructural study of the muscle coat of the gastric wall in a case of systemic sclerosis. Ann Rheum Dis. 61:754–756. 2002. View Article : Google Scholar : PubMed/NCBI

174 

Manetti M, Neumann E, Milia AF, Tarner IH, Bechi P, Matucci-Cerinic M, Ibba-Manneschi L and Müller-Ladner U: Severe fibrosis and increased expression of fibrogenic cytokines in the gastric wall of systemic sclerosis patients. Arthritis Rheum. 56:3442–3447. 2007. View Article : Google Scholar : PubMed/NCBI

175 

Pedersen J, Gao C, Egekvist H, Bjerring P, Arendt-Nielsen L, Gregersen H and Drewes AM: Pain and biomechanical responses to distention of the duodenum in patients with systemic sclerosis. Gastroenterology. 124:1230–1239. 2003. View Article : Google Scholar : PubMed/NCBI

176 

Latella G, Di Gregorio J, Flati V, Rieder F and Lawrance IC: Mechanisms of initiation and progression of intestinal fibrosis in IBD. Scand J Gastroenterol. 50:53–65. 2015. View Article : Google Scholar

177 

LeRoy EC, Trojanowska MI and Smith EA: Cytokines and human fibrosis. Eur Cytokine Netw. 1:215–219. 1990.PubMed/NCBI

178 

Babyatsky MW, Rossiter G and Podolsky DK: Expression of transforming growth factors alpha and beta in colonic mucosa in inflammatory bowel disease. Gastroenterology. 110:975–984. 1996. View Article : Google Scholar : PubMed/NCBI

179 

Kulkarni AB and Karlsson S: Transforming growth factor-beta 1 knockout mice. A mutation in one cytokine gene causes a dramatic inflammatory disease. Am J Pathol. 143:3–9. 1993.PubMed/NCBI

180 

Gorelik L and Flavell RA: Transforming growth factor-beta in T-cell biology. Nat Rev Immunol. 2:46–53. 2002. View Article : Google Scholar : PubMed/NCBI

181 

Meijer MJ, Mieremet-Ooms MA, van der Zon AM, van Duijn W, van Hogezand RA, Sier CF, Hommes DW, Lamers CB and Verspaget HW: Increased mucosal matrix metalloproteinase-1, -2, -3 and -9 activity in patients with inflammatory bowel disease and the relation with Crohn's disease phenotype. Dig Liver Dis. 39:733–739. 2007. View Article : Google Scholar : PubMed/NCBI

182 

Lakatos G, Hritz I, Varga MZ, Juhász M, Miheller P, Cierny G, Tulassay Z and Herszényi L: The impact of matrix metalloproteinases and their tissue inhibitors in inflammatory bowel diseases. Dig Dis. 30:289–295. 2012. View Article : Google Scholar : PubMed/NCBI

183 

Rath T, Roderfeld M, Graf J, Wagner S, Vehr AK, Dietrich C, Geier A and Roeb E: Enhanced expression of MMP-7 and MMP-13 in inflammatory bowel disease: A precancerous potential? Inflamm Bowel Dis. 12:1025–1035. 2006. View Article : Google Scholar : PubMed/NCBI

184 

Booms P, Pregla R, Ney A, Barthel F, Reinhardt DP, Pletschacher A, Mundlos S and Robinson PN: RGD-containing fibrillin-1 fragments upregulate matrix metallopro-teinase expression in cell culture: A potential factor in the pathogenesis of the Marfan syndrome. Hum Genet. 116:51–61. 2005. View Article : Google Scholar

185 

Booms P, Ney A, Barthel F, Moroy G, Counsell D, Gille C, Guo G, Pregla R, Mundlos S, Alix AJ and Robinson PN: A fibrillin-1-fragment containing the elastin-binding-protein GxxPG consensus sequence upregulates matrix metallopro-teinase-1: Biochemical and computational analysis. J Mol Cell Cardiol. 40:234–246. 2006. View Article : Google Scholar : PubMed/NCBI

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APA
Schrenk, S., Cenzi, C., Bertalot, T., Conconi, M.T., & Di Liddo, R. (2018). Structural and functional failure of fibrillin‑1 in human diseases (Review). International Journal of Molecular Medicine, 41, 1213-1223. https://doi.org/10.3892/ijmm.2017.3343
MLA
Schrenk, S., Cenzi, C., Bertalot, T., Conconi, M. T., Di Liddo, R."Structural and functional failure of fibrillin‑1 in human diseases (Review)". International Journal of Molecular Medicine 41.3 (2018): 1213-1223.
Chicago
Schrenk, S., Cenzi, C., Bertalot, T., Conconi, M. T., Di Liddo, R."Structural and functional failure of fibrillin‑1 in human diseases (Review)". International Journal of Molecular Medicine 41, no. 3 (2018): 1213-1223. https://doi.org/10.3892/ijmm.2017.3343