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Cartilage-oligomeric-matrix protein expression in systemic sclerosis reveals heterogeneity of dermal fibroblast responses to transforming growth factor-β
  1. Giuseppina Farina (farina{at}bu.edu)
  1. Boston University Medical Center, United States
    1. Raphael Lemaire (rlemaire{at}bu.edu)
    1. Boston University School of Medicine, United States
      1. Phillip Pancari (ppancari{at}bu.edu)
      1. Boston University, United States
        1. Julie Bayle (jbayle{at}bu.edu)
        1. Boston University, United States
          1. Russell L Widom (rwidom{at}bu.edu)
          1. Boston University, United States
            1. Robert A Lafyatis (lafyatis{at}bu.edu)
            1. Boston University Medical center, United States

              Abstract

              Objective: Cartilage Oligomeric Matrix Protein (COMP) accumulates in systemic sclerosis (SSc) skin and is upregulated by TGFβ. To further characterize 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 co-expressed 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 both COMP and SMA-expressing cells. COMP mRNA expression in lesional skin from dSSc patients correlated with the mRSS and TGFβ1 staining.

              Conclusion: These findings suggest that TGFβ upregulation of COMP and/or SMA expression in sub-populations 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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