Inflammation disrupts cholesterol efflux in human kidney mesangial cells via PPARγ-LXRα-ABCA1 pathway |
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| Authors: | CHEN Yu-yang CHEN Yao ZHAO Lei LI Qing RUAN Xiong-zhong CHEN Ya-xi |
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| Institution: | 1. Centre for Lipid Research, Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing 400016, China;
2. Center for Nephrology, Royal Free and University College Medical School, University College London, Royal Free Campus, London, UK |
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| Abstract: | AIM: To investigate the perturbative effects of inflammatory stress on cholesterol efflux in human kidney mesangial cells (HMCs) and the relation to peroxisome proliferators activated receptor-γ (PPARγ)-1iver X activated receptor-α (LXRα)-and ATP-binding cassette transporter A1 (ABCA1) pathway. METHODS: HMCs were cultured and divided into control group (incubated with serum free medium), high lipid group , inflammatory stress group or combination treatment group . The mRNA and protein levels of PPARγ, LXRα,ABCA1 were examined by real-time polymerase chain reaction (PCR) and Western blotting. cholesterol assay was performed to evaluate the efflux of cholesterol by liquid scintillation counter. Oil red O staining was used to evaluate lipid droplet accumulation in the cells. Intracellular cholesterol level was measured by enzymic assay. RESULTS: : LDL increased the expression of PPARγ, LXRα and ABCA1 at mRNA and protein levels in HMCs, while TNF-α reduced the expression of these genes at mRNA and protein levels. The cholesterol efflux was increased after LDL loading. However, inflammatory stress inhibited cholesterol efflux in the absence or presence of LDL loading. Oil red O staining and quantitative analysis showed that LDL loading increased the intracellular cholesterol level in HMCs and inflammatory stress further exacerbated the lipid accumulation. CONCLUSION: Inflammatory cytokine reduces cholesterol efflux by inhibiting the expression of PPARγ, LXRα and ABCA1, thereby causing lipid accumulation in HMCs. |
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| Keywords: | Inflammation Nuclear receptor ATP-binding cassette transporter A1 Human kidney mesangial cells Cholesterol efflux |
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