JNK-c-Jun信号通路下调连接蛋白43的表达引起肾小管上皮细胞转分化

目的 观察c-Jun氨基末端激酶（JNK）-c-Jun通路对连接蛋白43（Cx43）表达的影响及在转化生长因子（TGF）β1诱导的肾小管上皮细胞-肌成纤维细胞转分化（TEMT）中的作用。 方法　大鼠肾小管上皮细胞（NRK-52E）随机分成3组：对照组、TGF-β1（10 μg/L）组和TGF-β1（10 μg/L）+JNK选择性抑制剂SP600125（50 μmol/L）组。用免疫细胞化学、Western印迹检测JNK、c-Jun、连接蛋白43（Cx43）、上皮细胞标志物E-钙黏蛋白（E-cadherin）和肌成纤维细胞标志物α-SMA的表达。用RT-PCR检测Cx43的mRNA水平。用激光共聚焦显微镜荧光漂白恢复（FRAP）技术检测NRK-52E细胞间通讯功能。 结果 TGF-β1引起肾小管上皮细胞α-SMA、JNK、c-Jun表达上调（均P < 0.05），Cx43、E-cadherin表达下调（均P < 0.05），Cx43的mRNA水平下降（P < 0.05），细胞间通迅功能下降 （P < 0.05）。JNK抑制剂处理后，上述改变明显减轻。 结论 TGF-β1引起肾小管上皮细胞内JNK表达上调，增加c-Jun活性，从而抑制Cx43的表达和降低细胞间通迅功能，导致TEMT。

NK-c-Jun signal pathway induces tubular epithelial-myofibroblast transition via down-regulation of connexin 43 expression

Objective To explore the effect of JNK-c-Jun signal pathway on connexin 43 (Cx43) expression and its role in renal tubular epithelial-myofibroblast transition (TEMT) induced by TGF-β1. Methods Normal rat kidney tubular epithelial cells (NRK-52E) were cultured in Dulbecco's modified eagle medium (DMEM) with 10％ fetal bovine serum,then were randomly divided into 3 groups: control group,TGF-β1 group (treated with TGF-β1 10 μg/L),and TGF-β1+SP600125 (selective JNK inhibitor,50 μmol/L) group. The protein expressions of JNK,c-Jun,α-SMA,Cx43 and E-cadherin were assayed by immunocytochemistry and Western blotting.The Cx43mRNA was assayed by RT-PCR.Gap junction intercellular communication (CJIC) was measured by fluorescence recovery after photobleaching assay (FRAP). Results TGF-β1 increased the expressions of JNK,c-Jun and α-SMA (P＜0.05),reduced the expressions of Cx43 and E-cadherin (P＜0.05),and inhibited GJIC of NRK-52E (P ＜0.05).SP600125 could alleviate the above expressions changes and enhanced GJIC induced by TGF-β1. Conclusion JNK-c-Jun signal pathway induces TEMT of NRK-52E treated with TGF-β1 via down-regulation of connexin 43expression and inhibition of GJIC.