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.
| Gall, Jonathan M; Wang, Zhiyong; Liesa, Marc et al. (2012) Role of mitofusin 2 in the renal stress response. PLoS One 7:e31074 |
| Wang, Zhiyong; Gall, Jonathan M; Bonegio, Ramon G B et al. (2011) Induction of heat shock protein 70 inhibits ischemic renal injury. Kidney Int 79:861-70 |
| Gall, Jonathan M; Wong, Vincent; Pimental, David R et al. (2011) Hexokinase regulates Bax-mediated mitochondrial membrane injury following ischemic stress. Kidney Int 79:1207-16 |
| Wang, Zhiyong; Havasi, Andrea; Gall, Jonathan et al. (2010) GSK3beta promotes apoptosis after renal ischemic injury. J Am Soc Nephrol 21:284-94 |
| Havasi, Andrea; Wang, Zhiyong; Gall, Jonathan M et al. (2009) Hsp27 inhibits sublethal, Src-mediated renal epithelial cell injury. Am J Physiol Renal Physiol 297:F760-8 |
| Wang, Zhiyong; Havasi, Andrea; Gall, Jonathan M et al. (2009) Beta-catenin promotes survival of renal epithelial cells by inhibiting Bax. J Am Soc Nephrol 20:1919-28 |
| 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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