The role of Hedgehog signaling in fibrogenic liver repair.
Repair of adult liver, like many tissues, involves the coordinated response of a number of different cell types. In adult livers, fibroblastic cells, ductular cells, inflammatory cells, and progenitor cells contribute to this process. Our studies demonstrate that the fates of such cells are dictated, at least in part, by Hedgehog, a fetal morphogenic pathway that was once thought to be active mainly during embryogenesis. Studies of injured adult human and rodent livers demonstrate that injury-related activation of the Hedgehog pathway modulates several important aspects of repair, including the growth of hepatic progenitor populations, hepatic accumulation of myofibroblasts, repair-related inflammatory responses, vascular remodeling, liver fibrosis and hepatocarcinogenesis. These findings identify the Hedgehog pathway as a potentially important target for biomarker development and therapeutic manipulation, and emphasize the need for further research to advance knowledge about how this pathway is regulated by and interacts with other signals that regulate adult liver repair.
Division of Gastroenterology, Duke University Medical Center, Durham, NC 27710, USA.
Steve S
SS
Choi
Alessia
A
Omenetti
Wing-Kin
WK
Syn
Anna Mae
AM
Diehl
D000328:Adult; D000818:Animals; D019898:Autocrine Communication; D053823:Hedgehog Proteins / Q000502:physiology*; D006801:Humans; D008099:Liver / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008115:Liver Regeneration; D018919:Neovascularization, Physiologic; D019899:Paracrine Communication; D015398:Signal Transduction
D053823:Hedgehog Proteins