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Cartilage oligomeric matrix protein expression in systemic sclerosis reveals heterogeneity of dermal fibroblast responses to transforming growth factor β
  1. G Farina,
  2. R Lemaire,
  3. P Pancari,
  4. J Bayle,
  5. R L Widom,
  6. R Lafyatis
  1. Rheumatology Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA
  1. R Lafyatis, Boston University School of Medicine, Arthritis Center, E5, 715 Albany Street, Boston, Massachusetts, 02118, USA; lafyatis{at}bu.edu

Abstract

Objective: Cartilage oligomeric matrix protein (COMP) accumulates in systemic sclerosis (SSc) skin and is upregulated by transforming growth factor (TGF)β. To further characterise the response to TGFβ in SSc, we investigated TGFβ1 and COMP expression and myofibroblast staining in SSc skin.

Methods: Skin biopsies from patients with diffuse cutaneous SSc (dSSc), limited cutaneous SSc (lSSc) and healthy controls were evaluated for COMP mRNA expression using real-time PCR. COMP, α-smooth muscle actin (SMA) and TGFβ were assessed in skin sections and in cultured fibroblasts by immunohistochemistry. Clinical disease status was assessed by the modified Rodnan skin score (mRSS).

Results: Myofibroblasts expressing SMA and COMP were found coexpressed in many cells in dSSc dermis, but each also stained distinct cells in the dermis. Cultured SSc dermal fibroblasts also showed heterogeneity for COMP and SMA expression, with cells expressing SMA, COMP, both or neither. TGFβ treatment increased COMP and SMA-expressing cells. COMP mRNA expression in lesional skin from patients with dSSc correlated with the mRSS and TGFβ1 staining.

Conclusion: These findings suggest that TGFβ upregulation of COMP and/or SMA expression in subpopulations of fibroblasts contributes to different pathways of fibrosis and that multiple TGFβ regulated genes may serve as biomarkers for the degree of SSc skin involvement.

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Footnotes

  • Competing interests: None.

  • Funding: This study was supported by grants awarded to RL from the Scleroderma Foundation and the NIH: NIAMS Grant R01AR051089 and U01AR055063. This work was also supported by an NIH grant supporting the Boston University School of Medicine General Clinical Research Center Grant, M01 RR00533 and by an unrestricted grant from the American Society for Scleroderma Research.

  • Ethics approval: Ethics approval was obtained.

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