| First Author | Henderson NC | Year | 2006 |
| Journal | Proc Natl Acad Sci U S A | Volume | 103 |
| Issue | 13 | Pages | 5060-5 |
| PubMed ID | 16549783 | Mgi Jnum | J:107656 |
| Mgi Id | MGI:3621605 | Doi | 10.1073/pnas.0511167103 |
| Citation | Henderson NC, et al. (2006) Galectin-3 regulates myofibroblast activation and hepatic fibrosis. Proc Natl Acad Sci U S A 103(13):5060-5 |
| abstractText | 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. |
