肝细胞生长因子对人肾小管上皮细胞转分化的影响

Effects of HGF on the transdifferentiation of cultured human renal epithelial cells

目的 观察肝细胞生长因子(HGF)对转化生长因子β1(TGF β1)诱导的人肾小管上皮细胞(HKC)转分化的影响。方法 将体外培养的HKC分为正常组、TGF β1组、HGF组、TGF β1+HGF组、延迟加入HGF组。应用间接免疫荧光技术观察HKC中αSMA蛋白、E cadherin的表达。用RT PCR技术检测细胞中αSMA mRNA的表达。结果 免疫荧光技术显示,TGF β1 能诱导HKC表达αSMA蛋白,减少E cadherin表达;同时加入HGF能减少αSMA蛋白表达,而延迟加入HGF能使部分转分化的HKC细胞恢复E cadherin的表达。RT PCR结果显示,正常组无αSMA mRNA表达,TGF β1可诱导HKC表达αSMA mRNA;同时加入HGF后αSMA mRNA基本无表达,而延迟加入HGF后αSMA mRNA表达明显下降。结论 TGF β1可诱导肾小管上皮细胞转分化,而HGF能抑制TGF β1诱导的转分化,延迟加入HGF能使部分发生转分化的肾小管细胞恢复上皮表型。

Objective To examine the possible role of hepatocyte growth factor (HGF) in transdifferentiation induced by TGF β 1 in cultured human renal tubular epithelial cell lines(HKC). Methods The HKC cells were divided into negative control, positive control, HGF group, HGF inhibition group, HGF delayed administration group. Then the expression of E cadherin and alpha smooth muscle actin(α SMA)of HKC cells were assessed by indirect immunofluorescence ,the expression of α SMA mRNA of HKC cells were assessed by reverse transcriptase ploymerase chain reaction(RT PCR). Results HKC cells treated with TGF β 1 present a clear fibroblast like morphology, loss of epithelial marker E cadehrin and de novo expression of α SMA. Simultaneous incubation of HGF or delayed administration of HGF abrogated the α SMA expression and E cadherin depression triggered by TGF β 1 in HKC cells in a dose dependent manner. HGF also blocked morphologic transformation of tubular epithelial cells. Conclusion TGF β 1 is a key mediator that regulates the transdifferentiation of tubular epithelial cells into α SMA (+) myofibroblast, HGF can inhibit transdifferentiation of HKC cells induced by TGF β 1 , Delayed administration of HGF effectively suppresses, and partially reverses myofibroblastic transition of tubular epithelial cells