title: Increased serum levels and tissue expression of matrix metalloproteinase-12 in patients with systemic sclerosis: correlation with severity of skin and pulmonary fibrosis and vascular damage.
abstract: OBJECTIVE
  To determine serum concentrations and tissue expression of matrix metalloproteinase-12 (MMP-12) and their correlation with clinical features in patients with systemic sclerosis (SSc).
  
  
  METHODS
  Serum MMP-12 levels from 72 patients with SSc and 42 healthy volunteers were examined by ELISA. Immunohistochemical expression of MMP-12 was analysed in skin biopsies from 20 patients with SSc and 13 healthy subjects and lung biopsies from three patients with SSc-related interstitial lung disease (ILD) and five controls.
  
  
  RESULTS
  Circulating levels of MMP-12 were significantly increased in patients with SSc compared with healthy controls. Serum MMP-12 levels were significantly higher in both patients with limited cutaneous SSc and those with diffuse cutaneous SSc than in healthy controls, and correlated positively with the extent of skin involvement. MMP-12 levels were raised in SSc patients with ILD compared with patients without ILD, and correlated with severity of lung restriction. Increased serum levels of MMP-12 were also associated with the presence of digital ulcers and severity of nailfold capillary abnormalities. In contrast to almost undetectable MMP-12 expression in healthy skin, MMP-12 was strongly expressed in keratinocytes, dermal endothelial cells, fibroblasts/myofibroblasts and inflammatory cells in the skin of patients with SSc. Affected lung tissue from patients with SSc-related ILD showed strong MMP-12 expression in capillary vessels, inflammatory cells, alveolar macrophages and fibroblasts in the thickened alveolar septa, while faint expression was observed in normal lung tissue.
  
  
  CONCLUSIONS
  MMP-12 levels are increased in patients with SSc and are associated with severity of skin and pulmonary fibrosis and peripheral vascular damage.
authors.affiliation: Department of Anatomy, Histology and Forensic Medicine, University of Florence, Florence, Italy. mirkomanetti@yahoo.it
authors.forename: Mirko
authors.initials: M
authors.lastname: Manetti
authors.forename: Serena
authors.initials: S
authors.lastname: Guiducci
authors.forename: Eloisa
authors.initials: E
authors.lastname: Romano
authors.forename: Silvia
authors.initials: S
authors.lastname: Bellando-Randone
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Conforti
authors.forename: Lidia
authors.initials: L
authors.lastname: Ibba-Manneschi
authors.forename: Marco
authors.initials: M
authors.lastname: Matucci-Cerinic
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D005260:Female; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D053508:Matrix Metalloproteinase 12 / Q000097:blood*; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D011658:Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology*; D012595:Scleroderma, Systemic / Q000378:metabolism* / Q000473:pathology*; D012720:Severity of Illness Index; D012867:Skin / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; C507122:MMP12 protein, human; D053508:Matrix Metalloproteinase 12