Fibroblast abnormalities in the pathogenesis of systemic sclerosis

Expert Rev Clin Immunol. 2011 Jul;7(4):491-8. doi: 10.1586/eci.11.39.


Systemic sclerosis (SSc) is a chronic systemic disease characterized by autoimmunity, vascular lesions and progressive fibrosis. The fibrotic component is dominant in SSc compared with other vascular or autoimmune diseases and determines its prognosis and therapeutic refractoriness. Fibroblasts are responsible for abnormal extracellular matrix accumulation. Studies in cultured SSc skin fibroblasts have facilitated the identification of potential pathways involved in their profibrotic phenotype. Profibrotic fibroblasts characterized by abnormal growth and extracellular matrix synthesis may differentiate or expand from normal resident fibroblasts. Recruitment of bone marrow-derived progenitors and transdifferentiation of different cell lineages might also be involved. Multiple factors and signaling pathways appear to be involved in the development or persistence of the SSc fibroblast phenotype. Although their relative relevance and interplay are unclear, aberrant TGF-β signaling seems pivotal and constitutes the best characterized therapeutic target.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmunity / genetics
  • Cell Growth Processes / drug effects
  • Cell Transdifferentiation / drug effects
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Extracellular Matrix Proteins / metabolism
  • Fibroblasts / immunology*
  • Fibrosis / prevention & control
  • Humans
  • Molecular Targeted Therapy*
  • Scleroderma, Systemic / drug therapy
  • Scleroderma, Systemic / genetics
  • Scleroderma, Systemic / immunology*
  • Scleroderma, Systemic / physiopathology
  • Signal Transduction / drug effects
  • Skin / immunology
  • Skin / pathology*
  • Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / immunology*


  • Extracellular Matrix Proteins
  • Transforming Growth Factor beta