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Am J Physiol Gastrointest Liver Physiol 294: G595-G598, 2008. First published January 24, 2008; doi:10.1152/ajpgi.00543.2007
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THEMES

The Adventures of Sonic Hedgehog in Development and Repair. II. Sonic hedgehog and liver development, inflammation, and cancer

Alessia Omenetti1 and Anna Mae Diehl1

1Division of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, North Carolina

Submitted 19 November 2007 ; accepted in final form 20 January 2008

Hedgehog (Hh) signaling modulates tissue remodeling by controlling the fate of Hh-responsive cells. Healthy adult livers exhibit little Hh activity. However, cells involved in adult liver repair, including myofibroblasts and progenitors, are capable of producing and responding to Hh ligands. During adult liver injury, Hh ligand production increases and populations of Hh-responsive cells expand. This process is accompanied by fibrosis. Ligand production and Hh-responsive cells diminish as fibrosis resolves and normal hepatic architecture is restored, but Hh signaling persists in hepatocellular carcinomas. These findings suggest that the Hh pathway mediates remodeling responses that are triggered by adult liver damage.

hedgehog signaling; liver repair; stellate cells; liver fibrosis


Address for reprint requests and other correspondence: A. M. Diehl, Duke Univ. Medical Center, Div. of Gastroenterology, GSRB 1, 595 LaSalle St., Room 1073, Box 3256, Durham, NC 27710 (e-mail: annamae.diehl{at}duke.edu)




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