单核细胞与肾小管上皮细胞相互激活在肾间质纤维化中的作用

Effects of mutual activation of monocytes and renal proximal tubular epithelial cells on renal interstitial fibrosis

目的探讨单核细胞与肾小管上皮细胞相互激活在肾间质纤维化中的作用。方法体外共培养单核细胞(U937)与人近端肾小管上皮细胞(HK-2),观察U937细胞对HK-2细胞形态、上皮细胞间充质转分化(EMT)的影响及HK-2细胞对U937细胞分化的影响。结果 HK-2+U937细胞共培养24h,U937细胞可诱导HK-2细胞发生形态学转变。与单独培养HK-2细胞相比,HK-2+U937细胞(100×106个/ml)共培养24h可上调HK-2细胞EMT标记物α-平滑肌肌动蛋白(α-SMA)、纤维连接蛋白(FN)mRNA和蛋白表达,下调E-钙黏蛋白(E-cadherin)mRNA和蛋白表达(P<0.05或P<0.01)。与单独培养U937细胞相比,HK-2+U937细胞共培养可上调U937细胞M1标记物一氧化氮合酶(iNOs)mRNA表达,下调M2标记物精氨酸酶1(Arg-1)mRNA表达(P<0.05)。结论单核细胞可促进肾小管上皮细胞发生EMT,肾小管上皮细胞可促进单核细胞发生M1型转化,导致局部炎症反应放大,进一步促进肾间质纤维化。

Objective To study the effects of mutual activation of monocytes and renal proximal tubular epithelial cells on renal interstitial fibrosis.Methods The monocyte cells（U937）and human renal proximal tubular epithelial cells（HK-2）were co-cultured and the effects of U937 cells on morphological changes and epithelial mesenchymal transition（EMT）of HK-2cells and the effects of HK-2cells on the differentiation of U937 cells were observed.Results After co-cultured with U937 cells for 24 hours,HK-2cells developed a series of phenotypic changes.Compared with the separately cultured HK-2cells,the mRNA and protein expressions ofα-SMA and FN were up-regulated and E-cadherin was down-regulated when HK-2cells were co-cultured with U937cells（100×10^6pieces/ml）（P〈0.05 or P〈0.01）.Compared with the separately cultured U937 cells,the mRNA expression of iNOs was up-regulated and Arg-1was down-regulated when U937 cells were co-cultured with HK-2cells（P〈0.05）.Conclusion Monocyte cells can promote the EMT of renal tubular epithelial cells,and the renal tubular epithelial cells can promote monocyte cells M1 type transformation,which will amplify the local inflammatory reaction and promote the formation of renal interstitial fibrosis.