IGF-Ⅰ对人肾小管上皮细胞转分化相关基因表达的影响

Effects of insulin-like growth factor I on the expression of correlative genes of human renal tubular epithelial transdifferentiation

目的:探讨胰岛素样生长因子-Ⅰ(IGF-Ⅰ)在人肾小管上皮细胞转分化中的作用。方法:将体外培养的人肾小管上皮细胞(HK2)分为对照组和IGF-Ⅰ组:培养液中加入IGF-Ⅰ,终浓度分别为25、50、100、200ng/ml。倒置显微镜观察细胞形态变化。用逆转录-聚合酶链反应(RT-PCR)技术测定HK2细胞E-钙黏蛋白、角蛋白、α-平滑肌肌动蛋白(α-SMA)、波形蛋白和纤连蛋白(FN)mRNA水平的变化。结果:IGF-Ⅰ刺激使HK2细胞形态由椭圆变为梭形。不同浓度的IGF-Ⅰ作用于HK2细胞48h后E-钙黏蛋白和角蛋白mRNA的表达显著下降(P<0.05),α-SMA、波形蛋白和FNmRNA水平显著升高(P<0.01),且呈剂量依赖性。结论:IGF-Ⅰ在体外能刺激人肾小管上皮细胞向肌成纤维细胞(MyoF)转分化,并促进其合成细胞外基质(ECM)。

Objective： To investigate the role of insulin-like growth factor Ⅰ （IGF- Ⅰ ） in the transdifferentiation of human renal tubular epithelial cell line （HK2） in vitro. Methods： Cultured HK2 were divided into two groups： control group and IGF-Ⅰ group treated with IGF-Ⅰ of 25,50,100,200 ng/ml,respectively. The cell＇s morphological changes were traced with inverted microscope, and the expression of E-cadherin,keratin,α-smooth muscle actin （α-SMA）, vimentin and fibronectin （FN） mRNAs were detected by RT-PCR. Results： In HK2 cells, IGF-Ⅰ stimulated the oval-to-fusiform transdifferentiation in morphology,down-regulated E-cadherin and keratin mRNA expression （P 〈 0.05）,up-regulated vimentin,α-SMA and FN mRNAs expression （P 〈 0.01 ）. Conclusion： IGF-Ⅰ can induce the transdifferentiation of human renal tubular epithelial cells towards myofibroblasts （MyoF）,and stimulate the synthesis of extracellular matrix.