tailieunhanh - Báo cáo y học: "Expression of hepatocytic- and biliary-specific transcription factors in regenerating bile ducts during hepatocyte-to-biliary epithelial cell transdifferentiation"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Critical Care giúp cho các bạn có thêm kiến thức về ngành y học đề tài: Expression of hepatocytic- and biliary-specific transcription factors in regenerating bile ducts during hepatocyte-to-biliary epithelial cell transdifferentiation. | Limaye et al. Comparative Hepatology 2010 9 9 http content 9 1 9 COMPARATIVE HEPATOLOGY RESEARCH Open Access Expression of hepatocytic- and biliary-specific transcription factors in regenerating bile ducts during hepatocyte-to-biliary epithelial cell transdifferentiation 1 1 1 1 Pallavi B Limaye William C Bowen Anne Orr Udayan M Apte George K Michalopoulos Abstract Background Under compromised biliary regeneration transdifferentiation of hepatocytes into biliary epithelial cells BEC has been previously observed in rats upon exposure to BEC-specific toxicant methylene dianiline DAPM followed by bile duct ligation BDL and in patients with chronic biliary liver disease. However mechanisms promoting such transdifferentiation are not fully understood. In the present study acquisition of biliary specific transcription factors by hepatocytes leading to reprogramming of BEC-specific cellular profile was investigated as a potential mechanism of transdifferentiation in two different models of compromised biliary regeneration in rats. Results In addition to previously examined DAPM BDL model an experimental model resembling chronic biliary damage was established by repeated administration of DAPM. Hepatocyte to BEC transdifferentiation was tracked using dipetidyl dipeptidase IV DDPIV chimeric rats that normally carry DPPIV only in hepatocytes. Following DAPM treatment 20 BEC population turned DPPIV-positive indicating that they are derived from DPPIV-positive hepatocytes. New ductules emerging after DAPM BDL and repeated DAPM exposure expressed hepatocyte-associated transcription factor hepatocyte nuclear factor HNF 4a and biliary specific transcription factor HNF1p. In addition periportal hepatocytes expressed biliary marker CK19 suggesting periportal hepatocytes as a potential source of transdifferentiating cells. Although TGFp1 was induced there was no considerable reduction in periportal HNF6 expression as observed during embryonic .