Advanced glycation end product-induced peroxisome proliferator-activated receptor γ gene expression in the cultured mesangial cells

We identified the AGEs-induced expression of peroxisome proliferator-activated gamma (PPAR gamma) in the cultured mesangial cells using reverse transcriptionpolymerase chain reaction, electrophoretic mobility shift assay (EMSA), and Western immunoblotting. Administration of AG;Es-BSA into the cultured mesangial cells resulted in an increase in the levels of mRNA and proteins for PPAR gamma in a dose-dependent manner. Specific bands which indicate the protein binding to PPAR gamma responsive element (PPRE) in the nuclear extracts were also detected in AG;Es-BSA-treated mesangial cells, but not found in BSA-treated cells by EMSA, Antioxidants, NAG, PDTC, and aminoguanidine, attenuated the gene expression and activity of PPAR gamma induced by AC;Es, These results indicate that PPAR gamma was induced and activated by the oxidative signal(s) evoked by AG;Es-ligand-receptor interactions, AG;Es-induced gene expression of PPAR gamma and the signal intensity of PPAR gamma and PPRE complex were attenuated furthermore by protein kinase C inhibitors, calphostin C and staurospolin, but not abolished completely, indicating that both signal transduction pathways through the induction of PKC activation and independent of PKC activation were involved in the AGEs-mediated expression and activation process of PPAR gamma. AGEs also increased the gene expression of smooth muscle alpha-actin, which is a marker for phenotypic change in mesangial cells. It is suggested therefore that AGEs-induced transcription factor as the oxidative stress may have a role in the differentiation of mesangial cells. (C) 1999 Academic Press.