Role of p38 MAP kinase signal transduction in apoptosis and survival of renal epithelial cells.

The p38 MAP kinase signal transduction pathway is activated by various forms of cellular stress. While, in many tissues, activation of p38 MAP kinase is associated with apoptosis, in some tissues p38 activation is critical for survival. Oxalate deposits are associated with several pathological conditions that involve aberrant proliferation and cellular apoptosis. Studies from our laboratory demonstrated that exposure of renal epithelial cells to oxalate and COM-crystals resulted in activation of the p38 MAP kinase pathway. Moreover, the inhibition of the p38 MAO kinase pathway resulted in the inhibition of oxalate as well as COM-crystal-induced reinitiation of the DNA synthesis. These results suggest a critical role for the p38 MAP kinase pathway in pathological conditions associated with cellular proliferation and apoptosis following deposition of calcium oxalate.