Effects of TGF-beta s in the liver: cell proliferation and fibrogenesis

Ciba Found Symp. 1991;157:165-74; discussion 174-7. doi: 10.1002/9780470514061.ch11.


TGF-beta 1 is a potent inhibitor of hepatocyte proliferation in vivo and in culture and an inducer of fibrogenesis. It is produced by non-parenchymal cells in normal, regenerating, neoplastic and pre-neoplastic liver. TGF-beta 2 and beta 3 are also found in liver non-parenchymal cells and the amounts of their mRNAs increase during liver regeneration. TGF-beta 2 has similar effects to TGF-beta 1. Membranes from normal adult rat liver bind TGF-beta 1 with kinetics consistent with the presence of a single high affinity binding site; membranes from livers that have been regenerating for 12-72 hours show high affinity binding sites not detected in livers of normal or sham-operated rats. Affinity labelling of membranes from normal and regenerating liver shows two receptor proteins with Mr 85,000 and 65,000. In contrast, a prominent band corresponding to a binding protein of Mr 280,000 is detected in membrane preparations of cultured liver epithelial cells. Although modulation of TGF-beta 1 receptors occurs during liver regeneration, it has not been possible to determine which receptor is responsible for the TGF-beta 1 effects in hepatocytes. Other studies have demonstrated a significant correlation between TGF-beta 1 mRNA expression and various indicators of fibrogenesis in patients with chronic liver disease. Thus in animals and humans TGF-beta 1 appears to play a major role in the pathogenesis of fibrosis in chronic liver disease.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Cell Division / drug effects
  • Extracellular Matrix Proteins / biosynthesis
  • Fibrosis
  • Gene Expression Regulation / drug effects
  • Humans
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Liver Diseases / metabolism
  • Liver Neoplasms, Experimental / chemically induced
  • Liver Neoplasms, Experimental / metabolism
  • Liver Regeneration
  • RNA, Messenger / biosynthesis
  • Rats
  • Receptors, Cell Surface / metabolism
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta / biosynthesis
  • Transforming Growth Factor beta / pharmacology*
  • Transforming Growth Factor beta / physiology


  • Extracellular Matrix Proteins
  • RNA, Messenger
  • Receptors, Cell Surface
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta