Goals: The overall goals of this application are to examine the role of a the 13-catenin-Lef signaling pathway in contributing to the alterations in gene expression associated with acute renal injury and to elucidate the role of this pathway in modulating events associated with recovery of renal function.
Specific aims Each specific aims will test one of three interrelated hypotheses:
Specific aim 1 : To test the hypothesis that ATP depletion-repletion activates the Beta-catenin Lef pathway in cultured proximal tubular cells.
Specific aim 2 : To examine our hypothesis that ATP depletion-repletion results in beta-catenin-Lef mediated activation of gene expression.
Specific aim 3 : To test our hypothesis that the Beta-catenin-lef-1 pathway alone or in association with NF-kappB inhibits apoptosis induced by ATP depletion-repletion. Long-term goals: To elucidate the mechanisms involved in the process of recovery and repair from acute renal failure (ARF). Significance: Elucidation of the mechanisms involved in recovery and repair may lead to insight that facilitate the development of therapeutic interventions that promote recovery from ARF.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK052898-05
Application #
6545813
Study Section
General Medicine B Study Section (GMB)
Program Officer
Star, Robert A
Project Start
1998-07-01
Project End
2006-05-31
Budget Start
2002-07-01
Budget End
2003-05-31
Support Year
5
Fiscal Year
2002
Total Cost
$384,388
Indirect Cost
Name
Boston Medical Center
Department
Type
DUNS #
005492160
City
Boston
State
MA
Country
United States
Zip Code
02118
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Havasi, Andrea; Li, Zhijian; Wang, Zhiyong et al. (2008) Hsp27 inhibits Bax activation and apoptosis via a phosphatidylinositol 3-kinase-dependent mechanism. J Biol Chem 283:12305-13
Ruchalski, Kathleen; Mao, Haiping; Li, Zhijian et al. (2006) Distinct hsp70 domains mediate apoptosis-inducing factor release and nuclear accumulation. J Biol Chem 281:7873-80
Li, G; Yang, Q; Krishnan, S et al. (2006) A novel cellular survival factor--the B2 subunit of vacuolar H+-ATPase inhibits apoptosis. Cell Death Differ 13:2109-17
Lieberthal, Wilfred; Fuhro, Robert; Andry, Christopher et al. (2006) Rapamycin delays but does not prevent recovery from acute renal failure: role of acquired tubular resistance. Transplantation 82:17-22

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