title: Oxidized high-density lipoprotein impairs the function of human renal proximal tubule epithelial cells through CD36.
abstract: Unlike native high-density lipoprotein (HDL), oxidized HDL exerts adverse effects in a number of diseases, including chronic kidney disease (CKD); however, the mechanisms involved in this process remain unclear. In the present study, we investigated the effects of oxidized HDL on renal tubular cells, which play an important role in the progression of CKD. Human renal proximal tubule epithelial cells (HK-2) were cultured and stimulated with various concentrations of oxidized HDL in the absence or presence of CD36 siRNA. The results revealed that oxidized HDL enhanced the production of reactive oxygen species (ROS) and upregulated the expression of pro-inflammatory factors in the HK-2 cells in a dose-dependent manner. Incubation with oxidized HDL also increased the apoptosis of the HK-2 cells and reduced their migration ability in a dose‑dependent manner. Src family kinase, mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) were activated following stimulation with oxidized HDL. All these effects mediated by oxidized HDL on HK-2 cells were markedly attenuated by transfection with with CD36 siRNA pior to stimulation with oxidized HDL. These findings suggest that oxidized HDL enhances the pro-inflammatory properties and impairs the function of HK-2 cells, mainly through the scavenger receptor, CD36, as well as through the Src, MAPK and NF-κB pathways.
authors.affiliation: Kidney Institute of PLA, Department of Medicine, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.affiliation: Carder's Ward, No. 411 Hospital of PLA, Shanghai 200081, P.R. China.
authors.forename: Jianxiang
authors.initials: J
authors.lastname: Wu
authors.affiliation: Kidney Institute of PLA, Department of Medicine, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Kidney Institute of PLA, Department of Medicine, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Lili
authors.initials: L
authors.lastname: Fu
authors.affiliation: Kidney Institute of PLA, Department of Medicine, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Guiqun
authors.initials: G
authors.lastname: Wu
authors.affiliation: Kidney Institute of PLA, Department of Medicine, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Chenggang
authors.initials: C
authors.lastname: Xu
authors.affiliation: Kidney Institute of PLA, Department of Medicine, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Changlin
authors.initials: C
authors.lastname: Mei
mesh_terms: D017209:Apoptosis / Q000235:genetics; D018955:CD36 Antigens / Q000378:metabolism*; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000473:pathology; D008075:Lipoproteins, HDL / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000378:metabolism* / Q000473:pathology; D019061:src-Family Kinases
chemical_list: D018955:CD36 Antigens; D008075:Lipoproteins, HDL; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D019061:src-Family Kinases; D020928:Mitogen-Activated Protein Kinases