Peribiliary myofibroblasts in biliary type liver fibrosis.
Biliary type liver fibrosis develops as part of the wound healing response to bile duct injury in chronic cholestatic liver diseases. The origin of myofibroblasts accumulating together with extracellular matrix around proliferating bile duct structures (referred to as ductular reaction) in the setting of cholestatic injury, has been investigated mostly in the rat bile duct ligation model. Evidence indicates that hepatic stellate cells undergo a myofibroblastic transition following bile duct ligation and that myofibroblastic hepatic stellate cells disclose chemoattraction towards bile duct structures in cholestatic liver. On the basis of morphological studies, nevertheless, the origin of peribiliary myofibroblasts has also been attributed to the activation and proliferation of portal fibroblasts. Bile duct epithelial cells of the ductular reaction actively contribute to the promotion and regulation of biliary type liver fibrogenesis. They synthesize and release a number of paracrine mediators such as transforming growth factor-beta, connective tissue growth factor, platelet-derived growth factor-BB, and endothelin-1 that target different liver cell types, including hepatic stellate cells and portal fibroblasts. Through these interactions, bile duct epithelial cells and peribiliary myofibroblasts cause periportal fibrosis in cholestatic and also probably other types of liver diseases.
Kinnman
Nils
N
Department of Gastroenterology and Hepatology, Karolinska Hospital, Karolinska Institute, 171 76 Stockholm, Sweden. nils.kinnman@ks.se
Housset
Chantal
C
D000818:Animals; D001652:Bile Ducts / Q000166:cytology / Q000378:metabolism; D002633:Chemotaxis; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology*; D006133:Growth Substances / Q000502:physiology; D008099:Liver / Q000166:cytology; D008105:Liver Cirrhosis, Biliary / Q000209:etiology* / Q000473:pathology; D008954:Models, Biological; D011168:Portal System / Q000166:cytology; D051381:Rats
D006133:Growth Substances