The role of endothelin-1 signaling in the fibrosis observed in systemic sclerosis

Pharmacol Res. 2011 Jun;63(6):502-3. doi: 10.1016/j.phrs.2011.01.011. Epub 2011 Feb 17.


Scleroderma (systemic sclerosis, SSc) is an autoimmune disease of unknown etiology characterized by organ fibrosis. There is no therapy for SSc. However, a recent body of evidence strongly implicates endothelin-1 (ET-1) in the pathogenesis of SSc. ET-1 is found in abundance in SSc patients. ET-1 directly induces fibrogenic effects in vitro, and is required for the ability of TGFβ to induce fibrogenic effects both in vitro and in vivo. Moreover, endothelin receptor antagonism reverses key features of the persistent fibrotic phenotype of fibroblasts isolated from lesions of SSc patients. However, clinically, endothelin receptor antagonism alone has had mixed results. This minireview summarizes these observations.

Publication types

  • Review

MeSH terms

  • Animals
  • Endothelin-1 / metabolism
  • Endothelin-1 / physiology*
  • Fibrosis / drug therapy
  • Fibrosis / metabolism
  • Fibrosis / physiopathology*
  • Humans
  • Mice
  • Molecular Targeted Therapy
  • Scleroderma, Systemic / genetics
  • Scleroderma, Systemic / metabolism
  • Scleroderma, Systemic / physiopathology*
  • Signal Transduction
  • Transforming Growth Factor beta / physiology


  • Endothelin-1
  • Transforming Growth Factor beta