期刊
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
卷 290, 期 5, 页码 G859-G870出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00456.2005
关键词
Indian hedgehog; liver; patched; progenitor cell; sonic hedgehog
资金
- NIAAA NIH HHS [R01 AA 014243, R01 AA 010154, R01 AA 012059] Funding Source: Medline
- NIDDK NIH HHS [R01 DK 52851, R01 IP30-DK-065933, T32 DK 007713, R01 DK 053792] Funding Source: Medline
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.
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