DIFFERENT ACTIVATION OF MITOGEN-ACTIVATED PROTEIN-KINASES IN EXPERIMENTAL PROLIFERATIVE GLOMERULONEPHRITIS

Mitogen-activated protein (MAP) kinases are critical for cell signalin g goals such as cellular proliferation and induction of apoptosis. We examined whether MAP kinases, as a point of convergence for multiple e xtracellular stimuli, are activated in proliferative glomerulonephriti s (GN) in vivo. Accelerated crescentic anti-glomerular base ment membr ane (GBM) GN was induced in rats preimmunized with rabbit IgG by admin istration of rabbit anti-rat GEM serum. Whole cortical tissue and isol ated glomeruli were then subjected to kinase activity assays and Weste rn blot analysis. Cortical activity of the archetypal MAP kinase, extr acellular signal-regulated kinase (ERK), was increased significantly o ne: three, and seven days after induction of GN. In contrast, activati on of MAP kinases with antiproliferative actions, stress-activated pro tein kinase, and p38 MAP kinase was detectable only in the early stage s of proliferative GN (daps one and three), implying that different MA P kinases serve distinct roles in the pathogenesis of GN.