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

作　　者：Shenghua Wu Chao LU Ling Dong Ziqing Chen 

机构地区：[1]Department of Pediatrics,the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China [2]Central Laboratory, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China

出　　处：《Journal of Nanjing Medical University》2005年第5期223-226,共4页南京医科大学学报（英文版）

基　　金：135MedicalEmphasisgrantfromgovernmentofJiangsuProvince(2002-45)

摘　　要：Objective： To examine whether lipoxin A4 （LXA4） 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 LXA4 action. Methods： Glomerular mesangial cells of rat were cultured and preincubated with LXA4 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 （STAT3） were analyzed by electrophoretic mobility shift assay （EMSA）. Results： TNF-α-stimulated DNA synthesis of mesangial cells, upregulafion of cyclin E protein and STAT3 activities were inhibited by LXA4 in a dose-dependent manner. Conclusion： TNF-α-induced DNA synthesis of mesangial cells can be inhibited by TXA4 probably through the mechanism of Jak1/STAT3 pathway-dependent signal transduction.Objective： To examine whether lipoxin A4 （LXA4） 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 LXA4 action. Methods： Glomerular mesangial cells of rat were cultured and preincubated with LXA4 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 （STAT3） were analyzed by electrophoretic mobility shift assay （EMSA）. Results： TNF-α-stimulated DNA synthesis of mesangial cells, upregulafion of cyclin E protein and STAT3 activities were inhibited by LXA4 in a dose-dependent manner. Conclusion： TNF-α-induced DNA synthesis of mesangial cells can be inhibited by TXA4 probably through the mechanism of Jak1/STAT3 pathway-dependent signal transduction.

关 键 词：LIPOXIN tumor necrosis factor DNA synthesis CYCLIN STAT mesangial cell 

分 类 号：R692.6[医药卫生—泌尿科学]