title: Cartilage oligomeric matrix protein expression in systemic sclerosis reveals heterogeneity of dermal fibroblast responses to transforming growth factor beta.
abstract: 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 TGFbeta in SSc, we investigated TGFbeta1 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, alpha-smooth muscle actin (SMA) and TGFbeta 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. TGFbeta treatment increased COMP and SMA-expressing cells. COMP mRNA expression in lesional skin from patients with dSSc correlated with the mRSS and TGFbeta1 staining.
  
  
  CONCLUSIONS
  These findings suggest that TGFbeta upregulation of COMP and/or SMA expression in subpopulations of fibroblasts contributes to different pathways of fibrosis and that multiple TGFbeta regulated genes may serve as biomarkers for the degree of SSc skin involvement.
authors.affiliation: Rheumatology Section, Department of Medicine, Boston University School of Medicine, Arthritis Center, Boston, Massachusetts 02118, USA.
authors.forename: G
authors.initials: G
authors.lastname: Farina
authors.forename: R
authors.initials: R
authors.lastname: Lemaire
authors.forename: P
authors.initials: P
authors.lastname: Pancari
authors.forename: J
authors.initials: J
authors.lastname: Bayle
authors.forename: R L
authors.initials: RL
authors.lastname: Widom
authors.forename: R
authors.initials: R
authors.lastname: Lafyatis
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D064236:Cartilage Oligomeric Matrix Protein; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D064235:Matrilin Proteins; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D045743:Scleroderma, Diffuse / Q000378:metabolism / Q000473:pathology; D045745:Scleroderma, Limited / Q000378:metabolism / Q000473:pathology; D012595:Scleroderma, Systemic / Q000378:metabolism* / Q000473:pathology; D012720:Severity of Illness Index; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000502:physiology*
chemical_list: D000199:Actins; D015415:Biomarkers; D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins; D012333:RNA, Messenger; C577553:TSP5 protein, human; D053773:Transforming Growth Factor beta1