Galectin-3 Regulates Myofibroblast Activation and Hepatic Fibrosis

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2006 Mar 22

PMID 16549783

Citations 258

Authors

Neil C Henderson

Alison C MacKinnon

Sarah L Farnworth

Francoise Poirier

Francesco P Russo

John P Iredale

Christopher Haslett

Kenneth J Simpson

Tariq Sethi

Affiliations

Soon will be listed here.

Abstract

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.

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