Signaling in fibrosis: targeting the TGF beta, endothelin-1 and CCN2 axis in scleroderma

Front Biosci (Elite Ed). 2009 Jun 1;1:115-22.


Fibrosis affects organs such as the skin, liver, kidney and lung and is a cause of significant morbidity. There is no therapy for fibrosis. Recent significant molecular insights into the signaling underlying fibrosis have been made. Transforming growth factor beta (TGF beta) signaling is a major contributor to fibrogenesis. The signaling mechanisms through which TGF beta induces fibrogenic responses have been under intense scrutiny. Moreover, the potent pro-fibrotic proteins endothelin-1 (ET-1) and CCN2 (connective tissue growth factor, CTGF) are believed to play an essential role in this process as downstream regulators or co-factors of TGF beta signaling. This review summarizes these recent crucial observations with emphasis on the disease scleroderma.

Publication types

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

MeSH terms

  • Animals
  • Connective Tissue Growth Factor / metabolism*
  • Endothelin-1 / metabolism*
  • Fibrosis / metabolism*
  • Humans
  • Rats
  • Scleroderma, Systemic / metabolism*
  • Signal Transduction / physiology*
  • Transforming Growth Factor beta / metabolism*


  • CCN2 protein, human
  • Endothelin-1
  • Transforming Growth Factor beta
  • Connective Tissue Growth Factor