The role of IQGAP1 in high glucose-induced apoptosis of podocytes and its possible mechanisms

The apoptosis of podocytes may contribute to the development of diabetic nephropathy (DN). MAPK signaling pathway had a vital role in apoptosis. Meanwhile, IQ domain GTPase-activating protein 1 (IQGAP1) is an important scaffolding protein regulating MAPK signaling pathway. So we aimed to investigate the role of IQGAP1 under the medium of high glucose (HG). In vitro, human podocyte cells (HPC) were divided into 5 different groups named A-E and treated with glucose with normal concentration as control, mannitol, HG, HG with benazepril and HG with u0126, respectively. Expression of IQGAP1 was measured by quantitative real-time PCR (Q-PCR), western blotting and immunofluorescence assay, respectively. Apoptosis of HPC was detected by flow cytometry. The content of ERK1/2 and p-ERK1/2 were measured by western blotting. In vitro, HG suppressed the expression of IQGAP1, increased the level of p-ERK1/2 and contributed to the apoptosis of HPC. But benazepril, an angiotensin converting enzyme inhibitor, can attenuate the suppression of IQGAP1, down-regulated the level of p-ERK1/2 and attenuated the apoptotic rate of HPC caused by HG. Meanwhile, u0126, the ERK1/2 activation inhibitor, had no effect on HG induced suppression of IQGAP1, but significantly reduced the apoptotic rate of HPC. In conclusion, HG contributed to the apoptosis of HPC accompanied with the down-regulation of IQGAP1 and the increasing content of p-ERK. Benazepril could attenuate the HG-induced apoptosis of HPC and up-regulated the expression of IQGAP1.