Effect of Simvastatin on Lipid Accumulation and the Expression of CXCL16 and Nephrin in Podocyte Induced by Oxidized LDL

ABSTRACT

Objective: To investigate the effect of simvastatin on lipid accumulation and the expression of CXCL16 and Nephrin in murine podocytes induced by oxidized LDL (OxLDL) in order to explore the mechanism of protection. Methods: Murine podocytes (MPC5) were incubated with OxLDL (80 μg/ml) at different concentrations of simvastatin (0, 1.0, and 2.0 μg/ml) for 48 hours. Oil red O staining was used for the assessment of lipid accumulation in podocytes, and colorimetric cholesterol detection kit was used for the quantitative measurement. CXCL16 and Nephrin expression were detected by using Western blot. Results: OxLDL-treated MPC5 cells exhibited significantly higher intracellular lipid accumulations compared with the untreated group. Colorimetric detection found that total cholesterol was 90.3 ± 30.1 μg/ml in untreated cells and 226.5 ± 21.6 μg/ml in OxLDL-treated cells. The difference was statistically significant (p < .01). While cells were treated with both OxLDL and simvastatin, we observed little lipid accumulation. Total cholesterol in OxLDL + simvastatin cells were 151.8 ± 6.8 μg/ml and 135.5 ± 26.9 μg/ml under 1.0 μg/ml or 2.0 μg/ml of simvastatin treatment, respectively. Both were statistically significantly lower than that of the OxLDL treated cells (p < .05). Western blot analysis showed that CXCL16 expression was significantly increased (p < .05) in OxLDL-treated cells compared with the untreated cells, and was significantly inhibited by application of simvastatin (p < .05). The analysis of nephrin expression showed that there were no changes in group simvastatin compared with that of control group (p > .05). Nephrin expression was significantly reduced by treatment with OxLDL (p < .01), and was significantly increased by application of simvastatin (p < .05). Conclusion: Simvastatin treatment could significantly decrease lipid accumulation in murine podocytes and this protective effect was realized through inhibition of the expression of CXCL16 and increase in the expression of nephrin.

Keywords::

• oxidized low-density lipoprotein
• podocytes
• CXCL16
• nephrin
• simvastatin

FUNDING

This project was supported by the Provincial National Science Foundation of Shandong, #ZR2010HM110.