Jak_1/STAT_3 pathway mediates the inhibition of lipoxin A_4 on TNF-α-induced DNA synthesis of glomerular mesangial cells in rats

摘要

Objective: To examine whether lipoxin A_4(LXA_4) has an inhibitory effect on tumor necrosis factor-α(TNF-α)-induced DNA synthesis of glomerular mesangial cells of rat, and explore the molecular mechanisms of LXA_4 action. Methods: Glomerular mesangial cells of rat were cultured and preincubated with LXA_4 at different concentrations, and then treated with TNF-α(10 ng/ml). DNA synthesis was assessed by the incorporation of [~3H]-thymidine in mesangial cells. Expression of cyclin E protein was determined by Western blotting analysis. Activities of signal transducers and activators of transcription-3 (STAT_3) were analyzed by electrophoretic mobility shift assay (EMSA). Results: TNF-α-stimulated DNA synthesis of mesangial cells, upregulation of cyclin E protein and STAT_3 activities were inhibited by LXA_4 in a dose-dependent manner. Conclusion: TNF-α-induced DNA synthesis of mesangial cells can be inhibited by TXA_4 probably through the mechanism of Jak_1/STAT_3 pathway-dependent signal transduction.