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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
  1. Mirko Manetti1,
  2. Serena Guiducci2,
  3. Eloisa Romano2,
  4. Silvia Bellando-Randone2,
  5. Maria Letizia Conforti2,
  6. Lidia Ibba-Manneschi1,
  7. Marco Matucci-Cerinic2
  1. 1Department of Anatomy, Histology and Forensic Medicine, University of Florence, Florence, Italy
  2. 2Department of Biomedicine, Division of Rheumatology, AOUC and Excellence Centre for Research, Transfer and High Education DENOthe, University of Florence, Florence, Italy
  1. Correspondence to Dr Mirko Manetti, Department of Anatomy, Histology and Forensic Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy; mirkomanetti{at}


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.

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  • MM and SG contributed equally to this work.

  • LI-M and MM-C are joint senior authors.

  • Funding This study was supported by grants from the University of Florence (Progetti di Ricerca di Ateneo, ex 60% to LI-M and MM-C).

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval The study was approved by the local Institutional Review Board. The study complied with the principles of the Declaration of Helsinki and all subjects gave written informed consent.

  • Provenance and peer review Not commissioned; externally peer reviewed.