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Association between the MMP-12 gene and systemic sclerosis: role of RS2276109 functional polymorphism in the modulation of skin and pulmonary fibrosis
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  1. M Manetti1,2,
  2. L Ibba-Manneschi1,
  3. C Fatini3,
  4. S Guiducci2,
  5. A F Milia2,
  6. R Giacomelli4,
  7. S Bombardieri5,
  8. C Montecucco6,
  9. R Abbate3,
  10. G Valentini7,
  11. M 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, University of Florence, Florence, Italy
  3. 3Department of Medical and Surgical Critical Care, Thrombosis Centre, University of Florence, Florence, Italy
  4. 4Department of Internal Medicine and Public Health, Division of Rheumatology, University of L’Aquila, L’Aquila, Italy
  5. 5Division of Rheumatology, University of Pisa, Pisa, Italy
  6. 6IRCCS Policlinico San Matteo, University of Pavia, Italy
  7. 7Division of Rheumatology, II University of Naples, Naples, Italy

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Background

Systemic sclerosis (SSc) is a life-threatening autoimmune disease characterised by autoimmunity, widespread microvascular involvement and progressive fibrosis of the skin and internal organs. Recent evidence indicates that matrix metalloproteinase-12 (MMP-12) plays a critical role in pathological lung tissue remodelling and in transforming growth factor β-induced and bleomycin-induced pulmonary fibrosis. The authors have previously shown that different cell types (ie, fibroblasts and microvascular endothelial cells) isolated from the skin of patients with diffuse cutaneous SSc (dcSSc) constitutively overexpress and secrete MMP-12. Of …

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