Immunohistochemical analysis of TGF-β1 and VEGF in gingival and periodontal tissues: A role of these biomarkers in the pathogenesis of scleroderma and periodontal disease

  • Authors:
    • Giovanni Matarese
    • Gaetano Isola
    • Giuseppe Pio Anastasi
    • Angelo Favaloro
    • Demetrio Milardi
    • Giovanna Vermiglio
    • Giuseppe Vita
    • Giancarlo Cordasco
    • Giuseppina Cutroneo
  • View Affiliations

  • Published online on: June 11, 2012
  • Pages: 502-508
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Periodontal disease is characterized by inflammation and bone loss. The balance between inflammatory mediators and their counter-regulatory molecules may be fundamental for determining the outcome of the immune pathology of periodontal disease. Transforming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF) represent a family of polypeptide proteins involved in the inflammation and regulation of immune responses, especially in rheumatic disease. The relationship between these growth factors and periodontitis has resulted in a new field of osteoimmunology and provides a context for better understanding the pathogenesis of periodontal disease. Therefore, the aim of this study was to compare the protein expression profile of these inflammatory mediators in 90 patients divided in three groups: healthy control, chronic periodontitis and in rheumatic disease, scleroderma. The findings presented here highlight that biomarkers, such as TGF-β1 and VEGF, play a key role in the evolution of the immune response, which in turn influences the outcome of disease establishment.


Chronic periodontal disease is an inflammatory condition characterized by a shift in the microbial ecology of subgingival plaque biofilms and the progressive host-mediated destruction of tooth supporting structures (1). It can affect up to 90% of the world wide population: there are close connections between periodontal inflammation and major chronic condition, such as diabetes, heart disease and chronic autoimmune disease (2). The underlying mechanisms causing these pathological conditions are still unclear. Two mechanisms were proposed to explain this progression: bacteria acquire the ability to penetrate the deeper tissues (3), and/or the host response is degraded (4). In particular resident periodontal ligament and gingival fibroblasts have been reported to secrete matrix metalloproteinases (MMPs) and chemoattractants for epithelial cells (5). An important role in the inflammation during periodontal disease seems to also be played from different proteoglycans and glycosaminoglycans, such as syndecan 1 (6,7). The progression of inflammation and periodontal destruction requires a response to a bacterial insult that includes resident cells that sustain signals to trigger the immune response. Host-derived cytokines released upon microbial challenge have significant effects on the immune and inflammatory responses in periodontal disease (8,9); indeed, many cross-sectional studies have explored the production of Th1 and Th2 cytokines in human periodontitis (10,11). A prominent factor in connective tissue remodeling, and inflammatory diseases, is transforming growth factor-β (TGF-β): one of these isoforms, TGF-β1 is a multifunctional cytokine that regulates cell growth, differentiation and matrix production (12). It has potent immunosuppressive activity and downregulates the transcription of other pro-inflammatory cytokines, including interleukin-1, tumor necrosis factor-α and several metalloproteinases (13). TGF-β is a key mediator of tissue fibrosis and may lead to ECM accumulation in pathological states (14), moreover it mediates fibroblast activation, proliferation and signaling in cells cultures (15). The gene polymorphisms of this cytokine have been associated with risk for systemic diseases, including cardiovascular diseases and rheumatoid arthritis which are related to periodontitis (16).

In the development of chronic inflammatory disease, an important role is also played by the vascular endothelial growth factor (VEGF), a 45-kDa a homodimeric pro-inflammatory glycoprotein that potently increases microvascular permeability, promotes angiogenesis, and stimulates endothelial cell proliferation, migration, and survival (17); this protein seems to be involved in the onset and progression of gingivitis and periodontitis, mainly promoting the vascular network expansion generally observed in inflammation (18). Studies intended to associate the action of VEGF with the pathogenesis of periodontal disease have reported controversial findings. Nevertheless, VEGF expression is more strongly related to the healing stage of periodontal disease than to the destruction stage of the lesion (19).

In recent years, it has become apparent that patients with rheumatic diseases and periodontitis share common pathogenetic characteristics, such as a pro-inflammatory trait (20). Many reports have shown that periodontal disease is more common in rheumatoid arthritis (21), and that periodontal therapy reduces the severity of rheumatoid arthritis (22).

Systemic sclerosis (SSc) or scleroderma is a rheumatic acquired disorder that typically results in the fibrosis of the skin and internal organs (23). Previous findings indicate that the pathogenesis of this disorder includes inflammation, autoimmune attack, and vascular damage, leading to fibroblast activation (24,25). However, cultured SSc fibroblasts, which are free from such environmental factors, continue to produce the excessive amount of extracellular matrix (ECM) proteins, suggesting that SSc fibroblasts establish a constitutive self-activation system once activated (26).

The etiology of SSc remains uncertain, but one of the major cytokines that may be involved in this process is TGF-β1 (27), and the principal effect of this cytokine on mesenchymal cells is the stimulation of ECM deposition and angiogenesis alterations. We have already studied the distribution, by immunohistochemical analysis, of the major integrin and sarcoglycans subcomplex in bisphosphonate-induced osteonecrosis of the jaw (28), and the distribution of collagen I and IV into the periodontal ligament during orthodontic tooth movement (29) and for the first time, in the literature, we investigated the role of TGF-β1 and VEGF in the gingival tissues in the pathogenesis of rheumatic disease, SSc.

Therefore, the objective of the present study was to immunohistochemically determine the expression and distribution of TGF-β1 and VEGF in the gingival tissues and periodontal ligament of patients with chronic periodontitis (CP) and SSc compared to the healthy control group (CO).

Materials and methods

Patient selection

Ninety patients were enrolled in this crosssectional study performed from August 2010 and July 2011 at the University of Messina, Messina, Italy.

Thirty patients (5 male, 25 female, mean age 52.4, SD ±8.5), as defined by the American College of Rheumatology classification criteria for SSc were classified as diffuse SSc or limited SSc based on the extent of skin involvement (30). Disease onset was determined by patients’ recall of the first non-Raynaud symptom clearly attributable to scleroderma (31). Thirty patients with chronic adult periodontitis (11 male, 19 female, mean age 54, SD ±9.2) based on the criteria defined by the American Academy of Periodontology (32) and 30 healthy control subjects (16 male, 14 female, mean age 48.9, SD ±8.2) were enrolled. Therefore, the patients were divided in: CP, SSc and CO groups.

The protocol was approved by the Ethics and Research Committee of University of Messina, and ethical approval was obtained for the experimental procedures applied in humans, in accordance with the provisions of the World Medical Association’s Declaration of Helsinki of 1975, as revised in 2000. All patients included in the study signed an informed consent form. Patients with: diabetes mellitus, liver, kidney, or salivary gland dysfunction, history of alcoholism, a recent history or the presence of other acute or chronic infection, systemic antibiotic treatment or immunosuppressant medication (non SSc groups only) within previous three months, pregnancy and intense physical activity, smoking history or the presence of an oral mucosal inflammatory condition, were excluded from the study. Inclusion criteria included: ≥18 years of age who were in good general health (excluding the case definition) and had ≥18 erupted teeth.

The CP group had >30% of sites with bleeding on probing (BOP), >20% of sites with probing depth (PD) >4 mm, >10% of sites with interproximal clinical attachment level (CAL) >2 mm. The healthy control subjects had <10% sites with BOP <2% of sites with PD >5 mm, no sites with PD >6 mm, <1% of sites with CAL >2 mm and no radiographic bone loss (evident in posterior vertical bitewings films).

Clinical measurements

On each subject, plaque index (PI) (33), PD, clinical attachment level (CAL), community periodontal index of treatment needs (CPITN) (34) and presence of BOP were measured at 6 sites and recorded on each tooth. Every clinical periodontal measurement was performed by one calibrated examiner.

Gingival tissue biopsies

Gingival tissue and periodontal samples were carried out during routine erupted third molar extractions, advanced caries and orthodontic indications for the PD, SSc and healthy control groups. The collection of tissues of 2x2 mm in size were washed with saline solution and fixed in 10% neutral-buffered formalin, transported at 4°C and processed for immunohistochemistry.


From each biopsy, 25 sections were prepared. The samples were snap-frozen in liquid nitrogen and 20 μm sections were prepared in a cryostat for their use in a protocol to perform immunofluorescence. Finally, the sections were incubated with primary antibodies. The following primary antibodies were used: anti-TGF-β1 diluted 1:50 (sc146, Santa Cruz Biotechnology, Inc., Heidelberg, Germany), anti-VEGF diluted 1:50 (VG1, Novus Biologicals, Littleton, CO, USA). Primary antibodies were detected using Texas Red-conjugated IgG (Jackson ImmunoResearch Laboratories, Inc.). Slides were finally washed in PBS and sealed with mounting medium.

In the analysis, each specimen was divided into the following three areas to allow quantification of the distribution of cluster designation (CD) marked cells: i) the sulcular epithelium, ii) the middle area (lamina propria), and iii) the oral gingival epithelium. The investigations were conduced on 2,250 images by a blinded pathologist who performed the analysis in a blinded manner. The sections were then analyzed and images were acquired using a Zeiss LSM 5 DUO confocal laser scanning microscope (Carl Zeiss MicroImaging GmbH, Jena, Germany). All images were digitalized at a resolution of 8 bits into an array of 2,048x2,048 pixels. Optical sections of fluorescent specimens were obtained using a HeNe laser (wave-length, 543 nm) and an Argon laser (wavelength, 458 nm) at a 1-min 2-sec scanning speed with up to 8 averages; 1.50-μm sections were obtained using a pinhole of 250. Each image was acquired within 62 sec, in order to minimize photodegradation (Adobe Photoshop 7.0; Adobe Systems, Palo Alto, CA, USA).

Statistical analysis

Frequency distributions, median and standard deviation (SD) values were determined at baseline in each group to describe the clinical parameters (CAL, PD, CPITN, PI and BOP). The Kruskal-Wallis and the Mann-Whitney U tests were carried out when comparing the clinical parameters (CAL, PD and CPITN) in the three independent groups and the Wilcoxon singed rank test was used when comparing three matched-pair groups. The differences were considered statistically significant when P<0.05 (or 5%). The data were analyzed with software Prism (Graphpad Instat, version 5.00; GraphPad Software, San Diego, CA, USA).


A higher CAL (≥4 mm), PD site (≥5 mm) and PD values (<1), was observed in the SSc group compared with the controls (P<0.05); additionally, the BOP values (<1) were significantly higher in the SSc group than the healthy controls (P<0.05) (Fig. 1). Results are presented as the medians, confidence levels, lower and upper (L-U) quartiles (Table I). Higher levels of PI were observed in the CP compared to the CO group. BOP, as a measure of acute periodontal inflammation, was elevated in patients with CP compared to the CO group.

Table I.

Clinical characteristics of the patients at baseline (90 patients).

Table I.

Clinical characteristics of the patients at baseline (90 patients).

Healthy control
Chronic periodontitis
Clinical measurementn%n%n%
CAL (mm)
  >2.5 to <3.5620.026.61033.3
  ≥3.5 to <4.5--1860.01240.0
  CI (95%)214455
PD (mm)
  ≥2.5 to <3.5826.6516.6930.0
  ≥3.5 to <4.5--1653.31136.6
  CI (95%)22547
PI (value)
  >1 to <2413.32170.01550.0
  ≥2 to <3-930.0516.6
  CI (95%)203727
BOP (value)
  >1 to <2516.62170.01756.6
  ≥2 to <3--726.3310.0
  CI (95%)192737
CPITN (value)
  >1 to <213.31136.61756.6
  ≥2 to <3--1240.0413.3
  ≥3 to <4--310.0310.0
  CI (95%)183329

[i] PD, probing depth; CAL, clinical attachment level; PI, plaque index; BOP, bleeding on probing, CPITN, Community Periodontal Index of Treatment Needs; CI, confidence limit; L, lower quartile; U, upper quartile.

In order to investigate the relationship between gingival biomarker levels and clinical parameters of periodontal disease, we performed immunofluorescence reactions on gingival and periodontal ligament samples obtained from CO, CP and SSc, using antibodies against TGF-β1 and VEGF. First of all, we performed a negative control both on gingival samples with TGF-β1 (Fig. 2A) and VEGF (Fig. 2B) and periodontal ligament samples with TGF-β1 (Fig. 2C) and VEGF (Fig. 2D) using the secondary antibody only. Our results on gingival samples clearly showed a normal staining pattern for TGF-β1 in CO (Fig. 3A), whereas the staining was severely reduced in samples of patients with CP (Fig. 3B) and SSc (Fig. 3C). In contrast in immunofluorescence reactions performed using VEGF antibodies, staining patterns showed a higher intensity in CP (Fig. 3E) and SSc (Fig. 3F) than that observed in CO (Fig. 3D).

Similar results were obtained by immunof luorescence analysis of periodontal ligament (PDL) samples. Immunofluorescence reactions performed with TGF-β1, demonstrated that the staining signal was nearly absent in PDL obtained from patients affected by CP (Fig. 4B), and SSc (Fig. 4C) compared to PDL obtained from CO (Fig. 4A). Moreover immunofluorescence performed using the VEGF antibody revealed a higher staining pattern for VEGF in CP (Fig. 4E) and SSc (Fig. 4F) than that observed in CO (Fig. 4D). Furthermore, in periodontal diseases an increase of fluorescence was detected around the blood vessels (red circles in Fig. 4E and F).

Finally comparison of the clinical parameters between the studied groups, by statistical analysis, showed significantly higher differences in PD, CAL and CPITN, between patients with CP and SSc compared to CO.

There was a higher statistically significant difference (P<0.001) in the percentage of sites with CAL among the CP and SSc group and the control group (Fig. 1). There was no statistically significant difference at the PD sites between the CP and SSc group, but a statistically difference (P<0.05) in CAL between the CP and SSc group.


To study the role and the production of autocrine TGF-β1 and VEGF signaling, the production of these growth factors in CO, CP, SSc groups were examined, analyzing gingival and PDL biopsies obtained from each patient. Contrast and brightness were established by examining the most brightly labeled pixels and choosing the settings that allowed clear visualization of the structural details while keeping the pixel intensity at its highest (∼200).

This study showed that patients with CP and SSc had major severe periodontal disease in respect to the control group (Fig. 1). These studies also showed a particular relationship between periodontal disease and other chronic inflammatory diseases, such as SSc. These biomarkers contribute to sustaining the destructive inflammatory cascades seen in chronic periodontitis.

Transforming growth factor-β1 (TGF-β1) is known as one of the major anti-inflammatory cytokines (35). The large number of previous reports examining these polymorphisms of the TGF-β1 gene in various diseases reflects the interest in the role of this gene in chronic inflammatory diseases. Skaleric et al (36) found elevated TGF-β1 levels in gingival crevicular fluid samples from sites with deeper periodontal pockets.

Our results suggest that high TGF-β1 production may be a protective factor for periodontitis: potentially, this growth factor also accelerates connective tissue remodeling and angiogenesis (37): its biological activities result in insufficient remodeling and perfusion of tooth-supporting tissues contributing to periodontal destruction. However, previous reports rendered contradictory findings about the role of this growth factor (38).

Upregulation of TGF-β1 cytokine in patients with adult periodontitis may counterbalance the destructive gingival inflammatory responses in the acute phase of periodontitis (39). On the other hand, TGF-β1 was shown to induce chemotaxis for neutrophils, monocytes, mast cells and lymphocytes and is also an important mediator of the T-lymphocyte population (40).

Research to date has shown that TGF-β1 is mainly important in the early development stage of SSc (41). The main role in the fibrosis processes could be played by this growth factor, produced in excess by peripheral blood mononuclear cells (PBMC) (42).

TGF-β1 seems to be more significant in the fibrosis process than during the angiokinetic changes. TGF-β1 strongly slows down the PBMC adhesion to the endothelium and the generation of free radicals but can stimulate chemotaxis. Therefore, TGF-β1 may intensify inflammatory infiltrations around the vessels correlating with the beginning of the fibrosis process (43).

In addition, the present study clearly showed that VEGF expression was increased significantly in the destruction stage of the lesion, in contrast with a previous study that showed higher level of VEGF in the healing stage of the periodontal disease (19). Our study also showed that the mean concentrations of VEGF in periodontal tissues increased progressively from healthy to SSc subjects. This growth factor, in concert with TGF-β1, acts to stabilize the vascular wall and its imbalanced expression has been implicated in aberrant angiogenesis, a crucial factor in the pathogenesis of the SSc (44). However, angiogenesis in SSc is somewhat controversial. On one hand, Ozcelik et al (45) observed lower percentages of local VEGF expression in gingival biopsies of SSc patients when compared to the control group. On the other hand, Koch and Distler (46) showed, in accordance with our results, an increased production and stimulated neovascularization of VEGF in the blood vessels in the skin of SSc patients.

In conclusion, it is important to determine the exact function of these genetic polymorphisms during periodontitis in order to better understand their importance during disease progression. There is no doubt that we now have the technological basis to generate and analyze large volumes of information in the pursuit of understanding complex diseases such as periodontal disease at the molecular genetic level.

Our results suggest that TGF-β1 may contribute both to inflammatory regulation and remodeling events during periodontal disease. Therefore, we have documented that TGF-β1 downregulation in active periodontitis lesions has a key role in tissue destruction and bone resorption.

The findings presented here make it clear that biomarkers, such as TGF-β1 and VEGF play a key role in the evolution of the immune response in the periodontal and scleroderma disease, which in turn influences the outcome of disease establishment and evolution. It is important, therefore, to identify biomarkers that correlate with disease activity, prognosis and response to therapy allowing physicians to accurately identify patients early, those likely to respond and to predict prognosis of the disease.



PD MarshMicrobial ecology of dental plaque and its significance in health and diseaseAdv Dent Res826327119947865085


BL PihlstromBS MichalowiczNW JohnsonPeriodontal diseaseLancet1918091820200510.1016/S0140-6736(05)67728-8


DT GravesD FineYT TengTE Van DykeG HajishengallisThe use of rodent models to investigate host-bacteria interactions related to periodontal diseasesJ Clin Periodontol3589105200810.1111/j.1600-051X.2007.01172.x18199146


PM BartoldAS NarayananMolecular and cell biology of healthy and diseased periodontal tissuesPeriodontol 2000402949200610.1111/j.1600-0757.2005.00140.x16398684


WV GiannobileHost-response therapeutics for periodontal diseasesJ Periodontol7915921600200810.1902/jop.2008.08017418673015


S KotsovilisS Tseleni-BalafoutaA CharonisI FourmousisD NikolidakisJA VrotsosSyndecan-1 immunohistochemical expression in gingival tissues of chronic periodontitis patients correlated with various putative factorsJ Periodontal Res455205312010


AN AlexopoulouHA MulthauptJR CouchmanSyndecans in wound healing, inflammation and vascular biologyInt J Biochem Cell Biol39505528200710.1016/j.biocel.2006.10.01417097330


F D'AiutoM ParkarG AndreouJ SuvanPM BrettD ReadyMS TonettiPeriodontitis and systemic inflammation: control of the local infection is associated with a reduction in serum inflammatory markersJ Dent Res83156160200414742655


MA TaubmanT KawaiX HanThe new concept of periodontal disease pathogenesis requires new and novel therapeutic strategiesJ Clin Periodontol34367369200710.1111/j.1600-051X.2007.01065.x17448041


X HanT KawaiJW EastcottMA TaubmanBacterial-responsive B lymphocytes induce periodontal bone resorptionJ Immunol176625631200610.4049/jimmunol.176.1.62516365458


Q JinJA CirelliCH ParkJV SugaiM Taba JrPJ KostenuikWV GiannobileRANKL inhibition through osteoprotegerin blocks bone loss in experimental periodontitisJ Periodontol7813001308200710.1902/jop.2007.07007317608585


AB RobertsMB SpornTransforming growth factor betaAdv Cancer Res51107145198810.1016/S0065-230X(08)60221-3


H Birkadel-HansenRole of matrix metalloproteinases in human periodontal diseasesJ Periodontol64474484199310.1902/jop.1993.64.5.4748315570


KJ GordonGC BlobeRole of transforming growth factor-beta superfamily signaling pathways in human diseaseBiochim Biophys Acta1782197228200810.1016/j.bbadis.2008.01.00618313409


MC WilkesH MitchellSG PenheiterJJ DoreK SuzukiM EdensDK SharmaRE PaganoEB LeofTransforming growth factor-b activation of phosphatidylinositol 3-kinase is independent of Smad2 and Smad3 and regulates fibroblast responses via p21-activated kinase-2Cancer Res651043110440200510.1158/0008-5472.CAN-05-1522


F MercadoRI MarshallA KlestovPM BartoldRelationship between rheumatoid arthritis and periodontitisJ Periodontol72779787200110.1902/jop.2001.72.6.77911453241


F UnlüPG GüneriM HekimgilB YeşilbekH BoyacioğluExpression of vascular endothelial growth factor in human periodontal tissues: comparison of healthy and diabetic patientsJ Periodontol74181187200312666706


RB JohnsonFG SerioX DaiVascular endothelial growth factors and progression of periodontal diseasesJ Periodontol70848852199910.1902/jop.1999.70.8.84810476891


BO CetinkayaGC KelesB AyasEE SakalliogluG AcikgozThe expression of vascular endothelial growth factor in a rat model at destruction and healing stages of periodontal diseaseJ Periodontol7811291135200710.1902/jop.2007.06039717539728


PM BartoldRI MarshallDR HaynesPeriodontitis and rheumatoid arthritis: a reviewJ Periodontol7620662074200510.1902/jop.2005.76.11-S.206616277578


FB MercadoRI MarshallPM BartoldInter-relationships between rheumatoid arthritis and periodontal disease. A reviewJ Clin Periodontol30761772200310.1034/j.1600-051X.2003.00371.x12956651


MK Al-KatmaNF BissadaJM BordeauxJ SueAD AskariControl of periodontal infection reduces the severity of active rheumatoid arthritisJ Clin Rheumatol13134137200710.1097/RHU.0b013e318069061617551378


EC LeRoySystemic sclerosis (scleroderma)Cecil's Textbook of MedicineJB WyngaardenLH SmithJC Bennett19th editionSaunders WBPhiladelphia153015351992


JH KornImmunologic aspects of sclerodermaCurr Opin Rheumatol1479484198910.1097/00002281-198901040-000112702049


GA ScardinaME PizzigattiP MessinaPeriodontal micro-circulatory abnormalities in patients with systemic sclerosisJ Periodontol7619911995200510.1902/jop.2005.76.11.199116274320


A JelaskaM ArakawaG BroketaJH KornHeterogeneity of collagen synthesis in normal and systemic sclerosis skin fibroblasts: increased proportion of high collagen-producing cells in systemic sclerosis fibroblastsArthritis Rheum3913381346199610.1002/art.1780390811


EC LeRoyEA SmithMB KahalehM TrojanowskaRM SilverA strategy for determining the pathogenesis of systemic sclerosis: is transforming growth factor the answer?Arthritis Rheum3281782519892665755


E Nastro SiniscalchiG CutroneoL CatalfamoG SantoroA AllegraG OteriD CicciùA AlonciG PennaC MusolinoImmunohistochemial evaluation of sarcoglycans and integrins in gingival epithelium of multiple myeloma patients with bisphosphonate-induced osteonecrosis of the jawOncol Rep24129134201020514453


G AnastasiG CordascoG MatareseG RizzoR NuceraM MazzaA MilitiM PortelliG CutroneoA FavaloroAn immunohistochemical, histological, and electron-microscopic study of the human periodontal ligament during orthodontic treatmentInt J Mol Med215455542008


AT MasiSubcommittee for Scleroderma Criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria CommitteePreliminary criteria for the classification of systemic sclerosis (scleroderma)Arthritis Rheum23581590198010.1002/art.1780230510


B WhiteEA BauerLA GoldsmithGuidelines for Clinical Trials in Systemic Sclerosis (Scleroderma). I Disease-modifying interventions. The American College of Rheumatology Committee on Design and Outcomes in Clinical Trials in Systemic SclerosisArthritis Rheum383513601995


GC ArmitagePeriodontal diagnoses and classification of periodontal diseasesPeriodontology 200034921200410.1046/j.0906-6713.2002.003421.x14717852


J SilnessH LoePeriodontal disease in pregnancy. II Correlation between oral hygiene and periodontal conditionActa Odontol Scand22121135196410.3109/0001635640899396814158464


World Health OrganizationOral Health Surveys - Basic methodsCommunity Periodontal Index of Treatment Needs (CPITN)3rd edition3132Geneva1987


KJ TraceyPhysiology and immunology of the cholinergic antiin flammatory pathwayJ Clin Invest117289296200710.1172/JCI3055517273548


U SkalericB KramarM PetelinZ PavlicaSM WahlChanges in TGF-β1 levels in gingival, crevicular fluid and serum associated with periodontal inflammation in humans and dogsEur J Oral Sci1051361421997


JR MerwinJM AndersonO KocherCM Van ItallieJA MadriTransforming growth factor beta 1 modulates extra-cellular matrix organization and cell-cell junctional complex formation during in vitro angiogenesisJ Cell Physiol142117128199010.1002/jcp.1041420115


GV McDonnellCW KirkSA HawkinsCA GrahamLack of association of transforming growth factor (TGF)-beta 1 and beta 2 gene polymorphisms with multiple sclerosis (MS) in Northern IrelandMult Scler5105109199910335519


S SteinswollTS HalstensenK SchenkExtensive expression of TGF-β1 in chronically inflamed periodontal tissueJ Clin Periodontol263663731999


HW MittruckerSH KaufmannMini-review: regulatory T cells and infection: suppression revisitedEur J of Immunol34306312200410.1002/eji.20032457814768034


C QuerfeldB EckesC HuerkampT KriegS SollbergExpression of TGF-beta 1, -beta 2 and -beta 3 in localized and systemic sclerodermaJ Dermatol Sci211322199910.1016/S0923-1811(99)00008-010468187


H OtaS KumagaiA MorinobuH YanagidaK NakaoEnhanced production of transforming growth factor-beta (TGF-beta) during autologous mixed lymphocyte reaction of systemic sclerosis patientsClin Exp Immunol10099103199510.1111/j.1365-2249.1995.tb03609.x7697928


JL MehtaBC YangBS StratesP MehtaRole of TGF-beta1 in platelet-mediated cardioprotection during ischemia-reperfusion in isolated rat heartsGrowth Factors16179190199910.3109/0897719990900212810372959


A ArmulikA AbramssonC BetsholtzEndothelial/pericyte interactionsCirc Res97512523200510.1161/01.RES.0000182903.16652.d716166562


O OzcelikMC HaytacM ErginB AntmenG SeydaogluThe immunohistochemical analysis of vascular endothelial growth factors A and C and microvessel density in gingival tissues of systemic sclerosis patients: their possible effects on gingival inflammationOral Surg Oral Med Oral Pathol Oral Radiol Endod105481485200810.1016/j.tripleo.2007.07.021


AE KochO DistlerVasculopathy and disordered angiogenesis in selected rheumatic diseases: rheumatoid arthritis and systemic sclerosisArthritis Res Ther9Suppl 2S3200710.1186/ar218717767741

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September 2012
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Matarese G, Isola G, Anastasi GP, Favaloro A, Milardi D, Vermiglio G, Vita G, Cordasco G and Cutroneo G: Immunohistochemical analysis of TGF-β1 and VEGF in gingival and periodontal tissues: A role of these biomarkers in the pathogenesis of scleroderma and periodontal disease. Int J Mol Med 30: 502-508, 2012
Matarese, G., Isola, G., Anastasi, G.P., Favaloro, A., Milardi, D., Vermiglio, G. ... Cutroneo, G. (2012). Immunohistochemical analysis of TGF-β1 and VEGF in gingival and periodontal tissues: A role of these biomarkers in the pathogenesis of scleroderma and periodontal disease. International Journal of Molecular Medicine, 30, 502-508.
Matarese, G., Isola, G., Anastasi, G. P., Favaloro, A., Milardi, D., Vermiglio, G., Vita, G., Cordasco, G., Cutroneo, G."Immunohistochemical analysis of TGF-β1 and VEGF in gingival and periodontal tissues: A role of these biomarkers in the pathogenesis of scleroderma and periodontal disease". International Journal of Molecular Medicine 30.3 (2012): 502-508.
Matarese, G., Isola, G., Anastasi, G. P., Favaloro, A., Milardi, D., Vermiglio, G., Vita, G., Cordasco, G., Cutroneo, G."Immunohistochemical analysis of TGF-β1 and VEGF in gingival and periodontal tissues: A role of these biomarkers in the pathogenesis of scleroderma and periodontal disease". International Journal of Molecular Medicine 30, no. 3 (2012): 502-508.