Galectin-3 regulates myofibroblast activation and hepatic fibrosis

Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):5060-5. doi: 10.1073/pnas.0511167103. Epub 2006 Mar 20.


Central to fibrogenesis and the scarring of organs is the activation of fibroblasts into matrix-secreting myofibroblasts. We demonstrate that Galectin-3 expression is up-regulated in established human fibrotic liver disease and is temporally and spatially related to the induction and resolution of experimental hepatic fibrosis. Disruption of the Galectin-3 gene blocks myofibroblast activation and procollagen (I) expression in vitro and in vivo, markedly attenuating liver fibrosis. Addition of exogenous recombinant Galectin-3 in vitro reversed this abnormality. The reduction in hepatic fibrosis observed in the Galectin-3(-/-) mouse occurred despite equivalent liver injury and inflammation, and similar tissue expression of TGF-beta. TGF-beta failed to transactivate Galectin-3(-/-) hepatic stellate cells, in contrast with WT hepatic stellate cells; however, TGF-beta-stimulated Smad-2 and -3 activation was equivalent. These data suggest that Galectin-3 is required for TGF-beta mediated myofibroblast activation and matrix production. Finally, in vivo siRNA knockdown of Galectin-3 inhibited myofibroblast activation after hepatic injury and may therefore provide an alternative therapeutic approach to the prevention and treatment of liver fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon Tetrachloride / pharmacology
  • Fibroblasts
  • Galectin 3 / deficiency
  • Galectin 3 / genetics
  • Galectin 3 / metabolism*
  • Humans
  • Inflammation / genetics
  • Inflammation / metabolism
  • Inflammation / pathology
  • Liver / injuries
  • Liver / metabolism
  • Liver / pathology
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / metabolism*
  • Liver Cirrhosis / pathology*
  • Liver Cirrhosis, Experimental
  • Mice
  • Mice, Knockout
  • Muscle Cells / metabolism*
  • Muscle Cells / pathology*
  • RNA, Small Interfering / genetics
  • Rats
  • Signal Transduction
  • Smad Proteins / metabolism
  • Transforming Growth Factor beta / metabolism
  • Up-Regulation


  • Galectin 3
  • RNA, Small Interfering
  • Smad Proteins
  • Transforming Growth Factor beta
  • Carbon Tetrachloride