RESUMO
Objective To explore the effect and mechanism of fluvastatin on the expression of fibronectin(FN) in human peritoneal mesothelial cells (HPMCs) induced by high-glucose peritoneal dialysate (HGPDS).Methods Cultured HPMCs were randomly divided into control,HGPDS,HGPDS plus GSK650394 10-5 mol/L (the competitive inhibitor of SGK1),different concentrations of fluvastatin,fluvastatin 10-6 mol/L and GSK650394 10-5 mol/L alone.The morphology change of HPMC was observed by light microscopy.The cellular viability was detected by MTT colorimetry.The mRNA and protein expressions of serum and glucocorticoid-inducible kinase 1 (SGK1) and FN were detected by RT-PCR,Western blotting or ELISA.Results After incubation with HGPDS,the cell morphology changed from typical cobblestone-like appearance to fibroblast-like appearance,and the cell viability was inhibited significantly (P＜0.05).Fluvastatin 10-6mol/L and GSK650394 could improved the cell morphology and the cell viability injured by HGPDS (P＜0.05).Compared with the normal control group,the mRNA and protein expressions of SGK1 and FN increased significantly in HPMC treated with HGPDS(P＜0.05).GSK650394 significantly decreased the high expression of SGK1 and FN (P＜0.05),also the fluvastatin had same effects as GSK650394 in dose-dependent manner (P＜0.05).Conclusions High-glucose peritoneal dialysate can increase FN expression in human peritoneal mesothelial cells,which can be attenuated by fluvastatin.The protective role of fluvastatin in HPMC may be partially achieved through the signal pathway of SGK1.
RESUMO
Objective To investigate the cellular localization of the neural precursor cell-expressed, developmentally downregulated isoforms(Nedd4), Nedd4- 1/2 and Nedd4- 2, and the serum glucocorticoid- inducible kinasel(SGK1) in various subregions of the rat cochlea. Methods The expression patterns of Nedd4-1/2, Nedd42 and SGK1 in the cochlea of rat were studied by immunohistochemistry with the specific polyclonal rabbit antibodies against the rat Nedd4-1/2, Nedd4-2 and SGK1. Results All three proteins were extensively expressed in various regions of the rat cochlea. They were found in the stria vascularis, spiral ligament, organ of Corti, spiral limbus, spiral ganglion and Reissner's membrane. Conclusion Our findings suggest that there exists a Na+ transport system in the cochlea consisting of SGK1, Nedd4 isoforms and ENaC, which may work in concert to transport Na+ and to maintain homeostasis in the inner ear as they do in other tight epithelia.