Cartilage oligomeric matrix protein expression in systemic sclerosis reveals heterogeneity of dermal fibroblast responses to transforming growth factor β

Objective: Cartilage oligomeric matrix protein ( COMP) accumulates in systemic sclerosis (SSc) skin and is upregulated by transforming growth factor (TGF)beta. To further characterise the response to TGF beta in SSc, we investigated TGF beta 1 and COMP expression and myofibroblast staining in SSc skin. Methods: Skin biopsies from patients with diffuse cutaneous SSc (dSSc), limited cutaneous SSc (ISSc) and healthy controls were evaluated for COMP mRNA expression using real-time PCR. COMP, alpha-smooth muscle actin (SMA) and TGF beta 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. TGF beta treatment increased COMP and SMA-expressing cells. COMP mRNA expression in lesional skin from patients with dSSc correlated with the mRSS and TGF beta 1 staining. Conclusion: These findings suggest that TGF beta upregulation of COMP and/or SMA expression in subpopulations of fibroblasts contributes to different pathways of fibrosis and that multiple TGF beta regulated genes may serve as biomarkers for the degree of SSc skin involvement.