The Principal Investigator proposes to examine the effect of bile acids on cholangiocyte biology, based on the premise that chronic liver diseases with prominent cholestasis may be the result of injury directed towards the epithelial cells lining the biliary tree (cholangiocytes). Increased cholangiocyte secretion and proliferation are hallmarks of bile duct injury, and appear to be adaptive responses to injury. This occurs in the presence of elevated local levels of bile acids. With the recent discovery of the apical bile acid transporter (ABAT) in cholangiocytes, the question arises as to how bile acids modify cholangiocyte biology. The hypothesis is proposed that bile acids are internalized and affect intracellular signaling. The studies will determine the transcriptional regulation, translocation, and activity of ABAT in cholangiocytes; the potential for ABAT promoting the """"""""chole-hepatic shunt"""""""" for uptake of bile acids from bile back into the circulation within the liver will also be examined. The effect of bile acids on intracellular PKC, Ca++ and ERK signaling pathways will be determined. The differential effects of endogenous bile acids vs. therapeutic bile acids also will be examined. These studies will provide a better understanding of how bile acids interact with cholangiocytes, and hence may improve understanding of the cholangiocyte adaptation to injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK054208-05
Application #
6660836
Study Section
General Medicine A Subcommittee 2 (GMA)
Program Officer
Serrano, Jose
Project Start
2000-09-30
Project End
2005-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
5
Fiscal Year
2003
Total Cost
$223,618
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800771594
City
Houston
State
TX
Country
United States
Zip Code
77225
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