c-Jun N-terminal kinase-mediated AP-1 activation in experimental glomerulonephritis in rats.

We demonstrated activation of transcription factor AP-1 in rat nephrotoxic serum (NTS)-induced glomerulonephritis in a previous report. Here, we evaluate c-Jun N-terminal kinases (JNKs) activity to clarify the molecular mechanisms of AP-1 activation in nephritic glomeruli. Increased JNKs activity was detected in glomeruli isolated from NTS-treated rats. The kinetics of JNKs activation was similar to that of AP-1 activation. Phosphorylated c-Jun at Ser63, one of the target residues for JNK, was also detected in nephritic glomeruli. This is the first report demonstrating JNKs-mediated c-Jun/AP-1 activation in nephritic glomeruli. These results suggest an important role of the JNK-AP-1 signaling pathway in the pathogenesis of glomerulonephritis.