高糖对肾小球系膜细胞MKP-1蛋白表达泛素化调节的影响

Effects of high glucose on the expression of mkp-1 in glomerular mesangial cells via the ubiquitin-proteasome pathway

目的探讨高糖作用的肾小球系膜细胞MKP-1蛋白表达与泛素-蛋白酶体调节途径的关系。方法大鼠肾小球系膜HBZY-1细胞株分为8组,将高糖作为刺激因子,特异性泛素蛋白酶体抑制剂MG132作为干预因素。用蛋白免疫印迹法检测各组系膜细胞MKP-1的表达,实时定量PCR法检测各高糖组MKP-1mRNA的表达。结果高糖组系膜细胞MKP-1表达较正常血糖组均减少(P<0.05),各高糖组MKP-1 mRNA的表达差异无统计学意义(P>0.05),高糖组加入MG132后,系膜细胞MKP-1表达增加(P<0.05)。结论高糖可通过泛素蛋白酶体途径诱导肾系膜细胞MKP-1蛋白表达减少。提示泛素蛋白酶体途径参与了糖尿病肾病MAPK通路的信号调节。

[Objective] To explore the relationship between Ubiquitin-Proteasome Pathway （UPP） and MKP-1 in cultured rat glomernlar mesangial cells under high glucose. [Methods] Cultured HBZY-1 rat glomerular mesangial cells were divided into 8 groups, high glucose was a stimulated factor, MG132 was as an inhibitor of UPP. The expression of MKP-1 were measured by Western-blotting assay, the expression of MKP-1 mRNA were measured by real-time Quantitative PCR. [Results] Compared with normal glucose group, the expression of MKP-1 were decreased in high glucose groups （P〈O.05）, the expression of MKP-1 mRNA had no significant change in each group （P〉O.05）. The expression of MKP-1 in high glucose groups were increased obviously by adding MG132 （P〈0.05）. [Conclusion] High glucose can decrease significantly the expression of MKP-1 via the ubiquitin-proteasome pathway. UPP is involved in the regulation of MAPK signal pathways in diabetic nephropathy.