Oxidized high-density lipoprotein impairs the function of human renal proximal tubule epithelial cells through CD36

Gao,Xiang; Wu,Jianxiang; Qian,Yixin; Fu,Lili; Wu,Guiqun; Xu,Chenggang; Mei,Changlin

doi:10.3892/ijmm.2014.1799

Oxidized high-density lipoprotein impairs the function of human renal proximal tubule epithelial cells through CD36

Authors:
- Xiang Gao
- Jianxiang Wu
- Yixin Qian
- Lili Fu
- Guiqun Wu
- Chenggang Xu
- Changlin Mei
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Affiliations: Kidney Institute of PLA, Department of Medicine, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China, Carder's Ward, No. 411 Hospital of PLA, Shanghai 200081, P.R. China
Published online on: June 10, 2014 https://doi.org/10.3892/ijmm.2014.1799
Pages: 564-572

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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.

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