高糖通过下调PGC-1α激活NFAT并促进足细胞凋亡

发布时间：2018-04-29 07:24

本文选题：高糖 + 足细胞　；参考：《中国病理生理杂志》2017年04期

【摘要】：目的:足细胞凋亡在慢性肾病的发病发展中起着重要的作用,但目前对足细胞凋亡机制的研究还远未明确。本文旨在探讨过氧化物酶体增殖物激活受体γ共激活因子1α(PGC-1α)下调对足细胞凋亡的影响及其机制。方法:建立高糖诱导足细胞凋亡的体外模型,运用实时荧光定量PCR、Western blot、流式细胞术等方法分析高糖和PGC-1α沉默对足细胞凋亡以及相关分子mRNA和蛋白表达的影响。结果:在足细胞凋亡的体外模型中,PGC-1α表达显著下调。用siRNA沉默足细胞中的PGC-1α后,足细胞凋亡明显增加。核内活化T细胞核因子(NFAT)蛋白的表达在足细胞凋亡的体外模型也中明显增加,即NFAT活化;正常足细胞中沉默PGC-1α后NFAT也明显活化;在正常培养足细胞中沉默PGC-1α的同时沉默NFAT后,足细胞凋亡明显减轻。结论:PGC-1α的表达下调导致足细胞凋亡;NFAT可能介导了PGC-1α下调引起的足细胞凋亡。
[Abstract]:Objective: podocyte apoptosis plays an important role in the pathogenesis and development of chronic nephropathy, but the mechanism of podocyte apoptosis is far from clear. The aim of this study was to investigate the effect of down-regulation of peroxisome proliferator-activated receptor 纬 -co-activator 1 伪 (PGC-1 伪) on podocyte apoptosis and its mechanism. Methods: the model of podocyte apoptosis induced by high glucose was established in vitro. The effects of high glucose and PGC-1 伪 silencing on podocyte apoptosis and the expression of mRNA and protein were analyzed by real-time fluorescence quantitative PCR and flow cytometry. Results: the expression of PGC-1 伪 was significantly down-regulated in podocyte apoptosis model in vitro. The apoptosis of podocyte increased significantly after siRNA silencing PGC-1 伪 in podocyte. The expression of activated T cell nuclear factor (NFAT) protein was also significantly increased in the model of podocyte apoptosis in vitro, that is, NFAT activation, NFAT activation after PGC-1 伪 silencing in normal podocyte, and PGC-1 伪 silencing NFAT in normal podocyte. The apoptosis of podocyte was obviously alleviated. Conclusion the down-regulation of the expression of 10% PGC-1 伪 may lead to podocyte apoptosis. NFAT may mediate the apoptosis of podocyte induced by down-regulation of PGC-1 伪.
【作者单位】：深圳市龙岗区第二人民医院;
【基金】：深圳市科技创新委员会基金资助项目(No.JCYJ20160429173108762)
【分类号】：R692

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