pax2基因在肾小管上皮细胞转分化中的作用

Role of pax2 gene in renal tubular epithelial cell transdifferentiation.

目的探讨pax2基因在大鼠慢性肾小管间质纤维化过程中的表达及其对肾小管上皮细胞转分化的可能作用。方法大鼠5/6肾切除造模,分别于术后2、4、6、8、10、12周取左肾皮质,采用逆转录(RT)-PCR及免疫组织化学的方法检测模型组和正常对照组的pax2和-αSMA的表达。结果病变组织见系膜细胞和基质增生,间质炎症细胞浸润,基底膜变厚。5/6肾切除模型组大鼠在术后第2周出现pax2mRNA的强表达,第4周达高峰,与正常对照组比较P<0.05,此后下降至痕量表达;α-SMA mRNA也在术后第2周表达逐渐增强,第8周达高峰,与正常对照组比较P<0.05,此后逐渐下降。免疫组织化学染色显示,5/6肾切除模型组pax2蛋白的表达、肾小管上皮细胞中α-SMA的表达与pax2mRNA、α-SMA mRNA的表达趋势相同。结论在大鼠慢性肾间质纤维化的过程中,受损的肾小管上皮细胞可向肌成纤维细胞转分化,肾小管发育胚胎基因pax2在此过程中的一过性表达可能起到重要的作用。

Objective To observe the expression of the embryonic tubular epithelial cell developmental gene pax2 and its possible effect on renal tubular epithelial cell transdifferentiation in rat tubulointerstitial fibrosis. Methods The renal tubulointerstitial fibrosis model of Wistar rats was established by 5/6 nephrectomy. The left renal cortex was obtained for RT-PCR and immunochemistry assay at weeks 2, 4, 6, 8, 10 and 12 after operation. Results Renal pathologic analysis revealed that there was proliferation of cells and matrix, infiltration of many inflammatory cells in the interstitial tissue and basement membrane was thickened. In some renal tubular epithelial cells the expression of pax2 protein and mRNA was detected 2 weeks after operation in 5/6 nephrectomized rat model group, and peaked at 4th week after operation, then decreased, a-SMA showed similar tendency, but its peak time was 8 weeks after operation. Conclusion There is tubular epithelial celbmyofibroblast transdif-ferentiation in the process of renal tubulointerstitial fibrosis, in which embryonic tubular epithelial cell developmental gene pax2 may play a role.