Angiotensin Ⅱ induces lipid accumulation in human renal proximal tubular epithelial cells via the disruption of low density lipoprotein receptor pathway / 中华肾脏病杂志

ABSTRACT

Objective To investigate the effects of angiotensin Ⅱ (Ang Ⅱ) stimulating on cholesterol influx in human renal proximal tubular epithelial cells (HK-2) and the relation to low-density lipoprotein receptor (LDLr) pathway.Methods HK-2 cells were cultured and divided into the control group (incubated with serum-free medium) and Ang Ⅱ group (treated by 10-7 mol/L of Ang Ⅱ for 24 hours).The effects of Ang Ⅱ on lipid accumulation were examined by Oil red O staining and a quantitative assay of intracellular cholesterol.The expression of LDLr,sterol regulatory elementbinding protein (SREBP) cleavage activating protein (SCAP) and SREBP-2 mRNA and protein were examined by real-time PCR and Western blotting.The cotranslocation of SCAP-SREBP-2 from endoplasmic retieulum to Golgi in HK-2 cells was examined by immunofluorescent staining under confocal microscopy.Results Ang Ⅱ treatment increased intracellular lipid accumulation in HK-2 cells,which was associated with increased mRNA and protein expression of LDLr,SCAP,and SREBP-2 in HK-2 cells induced by Ang Ⅱ.Furthermore,results from confocal microscopy observation demonstrated that Ang Ⅱ increased the translocation of SCAP/SREBP-2 complex from endoplasmic reticulum to Golgi,thereby up-regulating LDLr gene transcription.Conclusion Ang Ⅱ disrupts LDLr feed-back regulation to increase cholesterol uptake and induce intracellular lipid accumulation.