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Cartilage oligomeric matrix protein expression in systemic sclerosis reveals heterogeneity of dermal fibroblast responses to transforming growth factor β
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Cartilage oligomeric matrix protein expression in systemic sclerosis reveals heterogeneity of dermal fibroblast responses to transforming growth factor β
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Journal Article
Cartilage oligomeric matrix protein expression in systemic sclerosis reveals heterogeneity of dermal fibroblast responses to transforming growth factor β
2009
Overview
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.
Publisher
BMJ Publishing Group Ltd and European League Against Rheumatism,BMJ Publishing Group
Subject
/ Adult
/ Biological and medical sciences
/ Biopsy
/ Cartilage Oligomeric Matrix Protein
/ Diseases of the osteoarticular system
/ Extracellular Matrix Proteins - genetics
/ Extracellular Matrix Proteins - metabolism
/ Female
/ Humans
/ Male
/ Scleroderma, Diffuse - metabolism
/ Scleroderma, Diffuse - pathology
/ Scleroderma, Limited - metabolism
/ Scleroderma, Limited - pathology
/ Scleroderma, Systemic - metabolism
/ Scleroderma, Systemic - pathology
