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Article

Decrease in matrix metalloproteinase‑3 activity in systemic sclerosis fibroblasts causes α2‑antiplasmin and extracellular matrix deposition, and contributes to fibrosis development

  • Authors:
    • Hirofumi Niwa
    • Yosuke Kanno
    • En Shu
    • Mariko Seishima
  • View Affiliations / Copyright

    Affiliations: Department of Dermatology, Gifu University Graduate School of Medicine, Gifu 501‑1194, Japan
  • Pages: 3001-3007
    |
    Published online on: July 28, 2020
       https://doi.org/10.3892/mmr.2020.11358
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Abstract

Systemic sclerosis (SSc) is a connective tissue disease of autoimmune origin characterized by fibrosis of the skin and visceral organs, and peripheral circulatory disturbance. α2‑antiplasmin (α2AP) is the major circulating inhibitor of plasmin and is a key regulator of fibrinolysis. It has been demonstrated that the expression of α2AP is elevated in dermal fibroblasts obtained from patients with SSc patients. It has also been determined that α2AP is associated with the development and progression of fibrosis in SSc. The present study assessed the relationship between α2AP and matrix metalloproteinase‑3 (MMP‑3), an extracellular matrix (ECM)‑degrading enzyme. Serum levels of α2AP and MMP‑3 were measured in healthy controls and patients with SSc using ELISA. No significant differences were determined between these two groups. α2AP, MMP‑3 and tissue inhibitor of metalloproteinase‑1 (TIMP‑1) expression was subsequently evaluated in normal and SSc fibroblasts via western blotting. The results revealed that α2AP expression increased in SSc dermal fibroblasts, while the ratio of MMP‑3/TIMP‑1 decreased. Additionally, incubation of recombinant α2AP with MMP‑3 caused α2AP degradation. The mixture of recombinant α2AP with MMP‑3 was subsequently added to normal fibroblasts prior to western blotting. The results revealed decreased α‑smooth muscle actin (α‑SMA; a marker of the myofibroblast phenotype) and type I collagen expression. The stimulation of SSc fibroblasts with MMP‑3 decreased protein levels of α2AP, α‑SMA and type I collagen, thus reversing the pro‑fibrotic phenotype of SSc fibroblasts. SSc fibroblast transfection with microRNA‑29a resulted in a decreased TIMP‑1 expression, but also decreased the protein expression of α2AP. The results indicated that MMP‑3 attenuated fibrosis progression by degrading α2AP and ECM, and might therefore contribute to a novel therapeutic approach for SSc treatment.
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1 

Gilbane AJ, Denton CP and Holmes AM: Scleroderma pathogenesis: A pivotal role for fibroblasts as effector cells. Arthritis Res Ther. 15:30012013. View Article : Google Scholar

2 

Collen D: Identification and some properties of a new fast-reacting plasmin inhibitor in human plasma. Eur J Biochem. 69:209–216. 1976. View Article : Google Scholar : PubMed/NCBI

3 

Kanno Y, Ishisaki A, Kawashita E, Kuretake H, Ikeda K and Matsuo O: uPA attenuated LPS-induced inflammatory osteoclastogenesis through the plasmin/PAR-1/Ca(2+)/CaMKK/AMPK axis. Int J Biol Sci. 12:63–71. 2016. View Article : Google Scholar : PubMed/NCBI

4 

Menoud PA, Sappino N, Boudal-Khoshbeen M, Vassalli JD and Sappino AP: The kidney is a major site of alpha(2)-antiplasmin production. J Clin Invest. 97:2478–2484. 1996. View Article : Google Scholar : PubMed/NCBI

5 

Kanno Y: The role of fibrinolytic regulators in vascular dysfunction of systemic sclerosis. Int J Mol Sci. 20:6192019. View Article : Google Scholar

6 

Kanno Y, Hirade K, Ishisaki A, Nakajima S, Suga H, Into T, Matsushita K, Okada K, Matsuo O and Matsuno H: Lack of alpha2-antiplasmin improves cutaneous wound healing via over-released vascular endothelial growth factor-induced angiogenesis in wound lesions. J Thromb Haemost. 4:1602–1610. 2006. View Article : Google Scholar : PubMed/NCBI

7 

Kanno Y, Kuroki A, Okada K, Tomogane K, Ueshima S, Matsuo O and Matsuno H: Alpha2-antiplasmin is involved in the production of transforming growth factor beta1 and fibrosis. J Thromb Haemost. 5:2266–2273. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Kanno Y, Kawashita E, Minamida M, Kaneiwa A, Okada K, Ueshima S, Matsuo O and Matsuno H: Alpha2-antiplasmin is associated with the progression of fibrosis. Am J Pathol. 176:238–245. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Kanno Y, Kawashita E, Kokado A, Okada K, Ueshima S, Matsuo O and Matsuno H: Alpha2-antiplasmin regulates the development of dermal fibrosis in mice by prostaglandin F(2α) synthesis through adipose triglyceride lipase/calcium-independent phospholipase A(2). Arthritis Rheum. 65:492–502. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Kanno Y, Kawashita E, Kokado A, Kuretake H, Ikeda K, Okada K, Seishima M, Ueshima S, Matsuo O and Matsuno H: α2AP mediated myofibroblast formation and the development of renal fibrosis in unilateral ureteral obstruction. Sci Rep. 4:59672014. View Article : Google Scholar : PubMed/NCBI

11 

Kanno Y, Ishisaki A, Kuretake H, Maruyama C, Matsuda A and Matsuo O: α2-antiplasmin modulates bone formation by negatively regulating osteoblast differentiation and function. Int J Mol Med. 40:854–858. 2017. View Article : Google Scholar : PubMed/NCBI

12 

Kawashita E, Kanno Y, Asayama H, Okada K, Ueshima S, Matsuo O and Matsuno H: Involvement of α2-antiplasmin in dendritic growth of hippocampal neurons. J Neurochem. 126:58–69. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Hou Y, Okada K, Okamoto C, Ueshima S and Matsuo O: Alpha2-antiplasmin is a critical regulator of angiotensin II-mediated vascular remodeling. Arterioscler. Thromb Vasc Biol. 28:1257–1262. 2008. View Article : Google Scholar

14 

Jinnin M, Ihn H, Yamane K, Asano Y, Yazawa N and Tamaki K: Plasma plasmin-alpha2-plasmin inhibitor complex levels are increased in systemic sclerosis patients with pulmonary hypertension. Rheumatology (Oxford). 42:240–243. 2003. View Article : Google Scholar : PubMed/NCBI

15 

Kawakami M, Kawagoe M, Harigai M, Hara M, Hirose T, Hirose W, Norioka K, Suzuki K, Kitani A and Nakamura H: Elevated plasma levels of alpha 2-plasmin inhibitor-plasmin complex in patients with rheumatic diseases. Possible role of fibrinolytic mechanism in vasculitis. Arthritis Rheum. 32:1427–1433. 1989. View Article : Google Scholar : PubMed/NCBI

16 

Kanno Y, Shu E, Kanoh H and Seishima M: The antifibrotic effect of α2AP neutralization in systemic sclerosis dermal fibroblasts and mouse models of systemic sclerosis. J Invest Dermatol. 136:762–769. 2016. View Article : Google Scholar : PubMed/NCBI

17 

Kanno Y, Shu E, Kanoh H, Matsuda A and Seishima M: α2AP regulates vascular alteration by inhibiting VEGF signaling in systemic sclerosis: The roles of α2AP in vascular dysfunction in systemic sclerosis. Arthritis Res Ther. 19:222017. View Article : Google Scholar : PubMed/NCBI

18 

Chen Q, Jin M, Yang F, Zhu J, Xiao Q and Zhang L: Matrix metalloproteinases: Inflammatory regulators of cell behaviors in vascular formation and remodeling. Mediators Inflamm. Jun 12–2013.(Epub ahead of print). View Article : Google Scholar

19 

Van Hove I, Lemmons K, Van de Velde S, Verslegers M and Moons L: Matrix metalloproteinase-3 in the central nervous system: A look on the bright side. J Neurochem. 123:203–216. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Nishijima C, Hayakawa I, Matsushita T, Komura K, Hasegawa M, Takehara K and Sato S: Autoantibody against matrix metalloproteinase-3 in patients with systemic sclerosis. Clin Exp Immunol. 138:357–363. 2004. View Article : Google Scholar : PubMed/NCBI

21 

Jinnin M, Ihn H, Asano Y, Yamane K, Yazawa N and Tamaki K: Serum matrix metalloproteinase-3 in systemic sclerosis. Arch Dermatol Res. 296:25–29. 2004. View Article : Google Scholar : PubMed/NCBI

22 

Young-Min SA, Beeton C, Laughton R, Plumpton T, Bartram S, Murphy G, Black C and Cawston TE: Serum TIMP-1, TIMP-2, and MMP-1 in patients with systemic sclerosis, primary Raynaud's phenomenon, and in normal controls. Ann Rheum Dis. 60:846–851. 2001.PubMed/NCBI

23 

Lijnen HR, Van Hoef B and Collen D: Inactivation of the serpin alpha(2)-antiplasmin by stromelysin-1. Biochim Biophys Acta. 1547:206–213. 2001. View Article : Google Scholar : PubMed/NCBI

24 

Bonaventura P, Lamboux A, Albarède F and Miossec P: Regulatory effects of zinc on cadmium-induced cytotoxicity in chronic inflammation. PLoS One. 12:e01808792017. View Article : Google Scholar : PubMed/NCBI

25 

Ciechomska M, O'Reilly S, Suwara M, Bogunia-Kubik K and van Laar JM: miR-29a reduces TIMP-1 production by dermal fibroblasts via targeting TGF-β activated kinase 1 binding protein 1, implications for systemic sclerosis. PLoS One. 9:e1155962014. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Niwa H, Kanno Y, Shu E and Seishima M: Decrease in matrix metalloproteinase‑3 activity in systemic sclerosis fibroblasts causes α2‑antiplasmin and extracellular matrix deposition, and contributes to fibrosis development. Mol Med Rep 22: 3001-3007, 2020.
APA
Niwa, H., Kanno, Y., Shu, E., & Seishima, M. (2020). Decrease in matrix metalloproteinase‑3 activity in systemic sclerosis fibroblasts causes α2‑antiplasmin and extracellular matrix deposition, and contributes to fibrosis development. Molecular Medicine Reports, 22, 3001-3007. https://doi.org/10.3892/mmr.2020.11358
MLA
Niwa, H., Kanno, Y., Shu, E., Seishima, M."Decrease in matrix metalloproteinase‑3 activity in systemic sclerosis fibroblasts causes α2‑antiplasmin and extracellular matrix deposition, and contributes to fibrosis development". Molecular Medicine Reports 22.4 (2020): 3001-3007.
Chicago
Niwa, H., Kanno, Y., Shu, E., Seishima, M."Decrease in matrix metalloproteinase‑3 activity in systemic sclerosis fibroblasts causes α2‑antiplasmin and extracellular matrix deposition, and contributes to fibrosis development". Molecular Medicine Reports 22, no. 4 (2020): 3001-3007. https://doi.org/10.3892/mmr.2020.11358
Copy and paste a formatted citation
x
Spandidos Publications style
Niwa H, Kanno Y, Shu E and Seishima M: Decrease in matrix metalloproteinase‑3 activity in systemic sclerosis fibroblasts causes α2‑antiplasmin and extracellular matrix deposition, and contributes to fibrosis development. Mol Med Rep 22: 3001-3007, 2020.
APA
Niwa, H., Kanno, Y., Shu, E., & Seishima, M. (2020). Decrease in matrix metalloproteinase‑3 activity in systemic sclerosis fibroblasts causes α2‑antiplasmin and extracellular matrix deposition, and contributes to fibrosis development. Molecular Medicine Reports, 22, 3001-3007. https://doi.org/10.3892/mmr.2020.11358
MLA
Niwa, H., Kanno, Y., Shu, E., Seishima, M."Decrease in matrix metalloproteinase‑3 activity in systemic sclerosis fibroblasts causes α2‑antiplasmin and extracellular matrix deposition, and contributes to fibrosis development". Molecular Medicine Reports 22.4 (2020): 3001-3007.
Chicago
Niwa, H., Kanno, Y., Shu, E., Seishima, M."Decrease in matrix metalloproteinase‑3 activity in systemic sclerosis fibroblasts causes α2‑antiplasmin and extracellular matrix deposition, and contributes to fibrosis development". Molecular Medicine Reports 22, no. 4 (2020): 3001-3007. https://doi.org/10.3892/mmr.2020.11358
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