Human Glomerular Mesangial Cells Of Type A Scavenger Receptor Expression And Simvastatin On Induction Of Scavenger Receptor Expression Role

In the early of last century, it was understood that dyslipidemia is a common complications of nephritic syndrome and chronic renal failure. The effect of dyslipidemia to promote the progression of renal disease has been accepted in the world wide since 1982, when Morhead published his paper 'Lipid nephrotoxicity in chronic progressive glomerular and tubulo-interstitial disease.^'[1] More and more authors recognized that oxidized low-density lipoprotein (Ox-LDL) plays an important role in glomerulosclerosis, althoμgh the mechanisms in this respect is still waiting for further disclose. In the study of atherosclerosis, it has been demonstrated that type A scavenger receptor (SR-A) mediates the uptake of modified low-density lipoproteins by macrophages. Ox-LDL facilitates the formation of arterial atheromatous plaques throμgh binding SR-A in macrophages. It is believed that glomerulosclerosis shared the similar mechanism with atherosclerosis; that is why to investigate the expression of SR-A and the role of Ox-LDL on human mesangial cell. The regulation effect of PMA, AngII and Ox-LDL on the expression of SR-A as well as potential effects of Simvastatin on inducible SCR has been done in cultured HMC and human mesangial cell line with high expression of SR-A in this study.Methods: To determine the function and binding properties of SR-A in HMC, human mesangial cell line (HMCL) with high expression of SR-A (HMCL-SR-A) was established after stable transfection of expressive vector with cDNA encoding SR-A. HMC, cultured in our Lab, were stimulated with PMA, Angll and Ox-LDL, uptake of fluorescence Dil-labeled acetylated LDL (Dil-Ac-LDL) and Ox-LDL by HMC were evaluated using con-focal microscopy and Oil Red "O" staining respectively. SCR mRNA expression was examined using reverse transcription- polymerase chain reaction (RT-PCR). Promoter activity of SR-A and signal transduction pathways in PMA or AngII-treated HMC were also assessed by transient expression assay.Results:1. More uptake of Ox-LDL and Ac-LDL has been observed in the HMCL-SR-A than that in the untransfected MHCL. Unlabeled Ox-LDL and Ac-LDL at a 40-fold excess concentration (200μg/ml) competed significantly with the uptake of Dil-Ac-LDL (5μg/ml) by HMC, otherwise this phenomenon was not observed when co-cultured with...