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。
AIM： To explore whether down-regulation of peroxisome proliferator-activated receptor γ coactivator（ PGC）-1α induces podocyte apoptosis and its mechanism. METHODS： The podocytes were cultured under high glucose（ HG） condition and the cell apoptosis was analyzed by flow cytometry. The methods of real-time PCR and Western blot were used to analyze the mRNA and protein expression of related molecules in the control,HG-treated or siRNA-treated podocytes.RESULTS： The expression PGC-1α at mRNA and protein levels was significantly decreased in HG-injured podocytes. Downregulation of PGC-1α expression in vitro by siRNA resulted in podocyte apoptosis. The nuclear protein expression of nuclear factor of activated T-cells（ NFAT） was significantly increased in HG injured podocytes,indicating the NFAT activation.Down-regulation of PGC-1α expression also decreased the nuclear protein expression of NFAT. Moreover,silencing of NFAT expression by siRNA significantly abolished PGC-1α deficiency-induced podocyte apoptosis. CONCLUSION：Down-regulation of PGC-1α induces podocyte apoptosis. NFAT mediates PGC-1α deficiency-induced podocyte apoptosis.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2017年第4期620-626,共7页
Chinese Journal of Pathophysiology
基金
深圳市科技创新委员会基金资助项目(No.JCYJ20160429173108762)
