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Role of hedgehog signalling in bile ductular cells
  1. Ian N Hines,
  2. Richard A Rippe
  1. Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, USA
  1. Dr R A Rippe, Division of Gastroenterology and Hepatology, Department of Medicine, 7340B MBRB, Campus Box # 7032, University of North Carolina, Chapel Hill, NC 27599, USA; rarippe{at}med.unc.edu

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Acute and chronic liver pathologies represent an important source of morbidity and mortality. Understanding the mechanisms of cell survival, repair and proliferation are critical to the development of future therapies for the treatment or prevention of liver disease of various aetiologies. Studies by Omenetti and colleagues published in this issue of Gut (see page 1275) identified increased hedgehog (Hh) signalling within the livers of bile duct ligated (BDL) rats.1 In these studies, sonic hedgehog (Shh) and Indian hedgehog (Ihh) were found to be increased during bile duct ligation in periportal epithelial cells expressing pan-cytokeratin, representing potential liver progenitor cell populations. When cholestasis was corrected, Shh expression and down-stream signalling progressively declined in a manner similar to platelet-derived growth factor expression which accompanied the resolution of tissue injury. Further, these studies identified the ability of Shh to promote survival of biliary epithelial cells possibly mediated through inhibition of caspase activity. The authors conclude from these studies that Hh signalling may represent an important protective factor within the damaged liver and may promote the survival of small periportal epithelial cells, potential hepatic progenitor cells. Indeed, these findings are a continuation of previous work by this group which demonstrated the presence of Hh signalling components in hepatic epithelial progenitor cells in patients with primary biliary cirrhosis.2 These studies are interesting …

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