title: Hedgehog signaling in cholangiocytes.
abstract: OBJECTIVE
  Cells lining the biliary tree are targets of injury, but also orchestrate liver repair. The latter involves autocrine/paracrine signaling that enhances the viability and growth of residual ductular cells and promotes accumulation of inflammatory and myofibroblastic cells. The mechanisms mediating this so-called 'ductular reaction' need to be better understood to improve injury outcomes. Studies are revealing that ductular cells produce and respond to hedgehog (Hh) ligands, developmental morphogens that control progenitor cell fate and tissue construction during embryogenesis. Because this has potential implications for liver repair, this review will summarize current knowledge about Hh signaling and cholangiocytes.
  
  
  RESULTS
  Diverse types of liver injury stimulate cholangiocytes to generate Hh ligands, and cholangiocyte-derived Hh ligands interact with receptors on cholangiocytes and neighboring cells to modulate virtually every aspect of the ductular reaction to injury. Excessive Hh signaling promotes dysfunctional repair and results in chronic hepatic inflammation, fibrogenesis, and carcinogenesis.
  
  
  CONCLUSIONS
  The Hh pathway is part of the complex signaling network that orchestrates liver repair. How other pathways and posttranscriptional mechanisms modulate Hh signaling in ductular cells remains unclear. Further research in this area may identify novel therapeutic targets for the treatment of cholangiopathies and cholangiocarcinoma.
authors.affiliation: Division of Gastroenterology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Alessia
authors.initials: A
authors.lastname: Omenetti
authors.forename: Anna Mae
authors.initials: AM
authors.lastname: Diehl
mesh_terms: D001659:Biliary Tract / Q000166:cytology* / Q000378:metabolism; D001660:Biliary Tract Diseases / Q000378:metabolism*; D018281:Cholangiocarcinoma / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D053823:Hedgehog Proteins / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000166:cytology* / Q000378:metabolism*; D008107:Liver Diseases / Q000378:metabolism; D010641:Phenotype; D015398:Signal Transduction / Q000502:physiology
chemical_list: D053823:Hedgehog Proteins