Gene expression associated with acute renal injury: (Drs. Borkan and Schwartz)

The overall goals of these studies are to examine the role of a the b-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. We will test three interrelated hypotheses: 1: To test the hypothesis that ATP depletion-repletion activates the b–catenin-Lef pathway in cultured proximal tubular cells. 2: To examine our hypothesis that ATP depletion-repletion results in b–catenin-Lef mediated activation of gene expression. 3: To test our hypothesis that the b-catenin-lef-1 pathway alone or in association with NF-kB 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.

References:

  1. Diviya Sinha, Zhiyong Wang, Valerie R. Price, John H. Schwartz, and Wilfred Lieberthal. Chemical anoxia of tubular cells induces activation of c-Src and its translocation to the zonula adherens . Am J Physiol Renal Physiol 284: F488-F497, 2003
  2. Diviya Sinha, Saswati Bannergee, John H. Schwartz, Wilfred Lieberthal, and Jerrold S. Levine Inhibition of ligand-independent ERK1/2 activity in kidney proximal tubular cells deprived of soluble survival factors upregulates Akt and prevents apoptosis. J Biol Chem 279:10962-10972, 2004
  3. Sinha D, Wang Z, Ruchalski KL, Levine JS, Krishnan S, Lieberthal W, Schwartz JH, and Borkan SC. Lithium activates the Wnt and phosphatidylinositol 3-kinase Akt signaling pathways to promote cell survival in the absence of soluble survival factors. Am J Physiol Renal Physiol, 288: F703–F713, 2005

Primary teaching affiliate
of BU School of Medicine