Simvastatin Improve ADAMTS13 mRNA and Protein Expression in Podocytes.

ADAMTS13 is a specific VWF (von Willebrand factor) -cleaving protease, which severe deficiency is the main cause of thrombotic thrombocytopenic purpura. ADAMTS13 is mainly synthesized and released of the surface of hepatic stellate cells and endothelial cells, but is alsoexpressed in other cells, including kidneypodocytes. Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, not only has benefit action on atherosclerosis but also has anti-inflammatory and antithrombotic properties. Recent study indicated that ADAMTS13 can reduce inflammatory plaque formation during early atherosclerosis in mice. In this study, we investigate the effects of simvastatinon inflammatory factors-induced ADAMTS13 expression in podocytes.

A conditionally immortalized mouse podocyte cell line was used in the study. Inflammatory factors (TNF-Á, IL-4, IL-6) and simvastatin were added to cell culture medium to exam their effect on ADAMTS13expresion in podocytes. We examedADAMTS13mRNA and protein expressbyquantitative real-time PCR (qRT-PCR) and Western blotting.

Our results showed that ADAMTS13 mRNA and protein was expressed in podocytes, and its expression levels were significantly decreased in cells treated withdifferent concentrations of IL-4 (1, 5,10 ng/mL) and IL-6(1,10, 100 ng/mL), while TNF-Á almost had no effect on ADAMTS13 expression. When podocytes treated with simvastatin (1 and 10 Ìmol/L), ADAMTS13 mRNA were significantly increased (1.53 ± 0.80 and 3.46 ±1.70, respectively, p<0.01 vs control), and ADAMTS13 protein levels were also increased (2.05 ± 0.18 and 2.22±0.12, respectively, p<0.01 vs control). Simvastatin also can reverse the inhibition effect of IL-6 (100 ng/mL) and IL-4 (10 ng/mL) on ADAMTS13 mRNA and protein expression in podocytes in a dose-independent manner.

We demonstrate that different inflammatory cytokines had different influence on ADAMTS13's expression in podocytes. Simvastatin can increase the expression of ADAMTS13 in a dose-dependent manner with or without IL-6 and IL-4, which may be a very relevant compartment for the antithrombotic property of simvastatin.

No relevant conflicts of interest to declare.