肝细胞生长因子负性调控细胞转分化在肾间质纤维化中的作用

目的 研究肝细胞生长因子(HGF)对单侧输尿管梗阻(UUO)大鼠肾间质纤维化的保护作用及其可能机制｡方法 大鼠随机分为UUO组､HGF治疗组和假手术组｡用实时荧光定量RT-PCR､Western杂交和免疫组化检测术后大鼠肾组织结缔组织生长因子(CTGF)和骨形成蛋白7(BMP7)表达量｡免疫组化检测大鼠肾组织TGF-β1､FN及α-SMA表达｡结果 与假手术组相比,UUO组及HGF治疗组CTGF mRNA､TGF-β1､α-SMA､FN､CTGF蛋白表达均增高,且UUO组明显高于治疗组;UUO组及HGF治疗组BMP7 mRNA和蛋白表达均减少,且UUO组显著低于治疗组｡结论 HGF能减轻肾间质纤维化,负性调控肾小管上皮细胞-肌成纤维细胞转分化,调节CTGF及BMP7表达可能是其作用途径｡

Identification and characterization of hepatocyte growth factor in counteracting tubular epithelial- myofibroblast transdifferentiation in renal interstitial fibrosis

Objective To investigate the protective effect of hepatocyte growth factor (HGF) and its mechanism on renal interstitial fibrosis following unilateral ureteral obstruction(UUO) in rat kidney. Methods Rats were randomly assigned to UUO group, HGF treated group and sham-operation group(SOR). HGF was administered by peritoneal injection into rat with renal fibrosis disease induced by UUO. The levels of BMP7 and CTGF mRNA were examined by RT-PCR. The sites and the expression of BMP7 and CTGF were examined by immunohistochemistry staining and Western blotting. The protein expression of TGF-β1,α-SMA, and FN was detected by immunohisto-chemistry at each time point. Results The mRNA and the protein levels of BMP7 were significantly lower in UUO group than those in HGF treated group, whereas the mRNA and protein levels of CTGF were significantly increased in UUO group. Compared to UUO group, the levels of TGF-β1, α-SMA and FN were significantly decreased in tubulointerstitium of HGF treated group. Conclusion HGF counteractes renal interstitial fibrosis by blocking tubular epithelialmyofibroblast transdifferentiation through down-regulation of CTGF and up-regulation of BMP7 in vivo.