Hedgehog signaling maintains resident hepatic progenitors throughout life.

Published

Journal Article

Hedgehog signaling through its receptor, Patched, activates transcription of genes, including Patched, that regulate the fate of various progenitors. Although Hedgehog signaling is required for endodermal commitment and hepatogenesis, the possibility that it regulates liver turnover in adults had not been considered because mature liver epithelial cells lack Hedgehog signaling. Herein, we show that this pathway is essential throughout life for maintaining hepatic progenitors. Patched-expressing cells have been identified among endodermally lineage-restricted, murine embryonic stem cells as well as in livers of fetal and adult Ptc-lacZ mice. An adult-derived, murine hepatic progenitor cell line expresses Patched, and Hedgehog-responsive cells exist in stem cell compartments of fetal and adult human livers. In both species, manipulation of Hedgehog activity influences hepatic progenitor cell survival. Therefore, Hedgehog signaling is conserved in hepatic progenitors from fetal development through adulthood and may be a new therapeutic target in patients with liver damage.

Full Text

Duke Authors

Cited Authors

  • Sicklick, JK; Li, Y-X; Melhem, A; Schmelzer, E; Zdanowicz, M; Huang, J; Caballero, M; Fair, JH; Ludlow, JW; McClelland, RE; Reid, LM; Diehl, AM

Published Date

  • May 2006

Published In

Volume / Issue

  • 290 / 5

Start / End Page

  • G859 - G870

PubMed ID

  • 16322088

Pubmed Central ID

  • 16322088

Electronic International Standard Serial Number (EISSN)

  • 1522-1547

International Standard Serial Number (ISSN)

  • 0193-1857

Digital Object Identifier (DOI)

  • 10.1152/ajpgi.00456.2005

Language

  • eng