Podocyte apoptosis plays a pivotal role in the pathogenesis of diabetic nephropathy (DN). The main purpose of this study was to investigate the effects of perilipin2 on high glucose (HG)-induced podocyte apoptosis and associated mechanisms. Differentially expressed genes (DEGs) in BTBR ob/ob mice vs. nondiabetic mice kidneys were obtained from GSE106841 dataset and picked out using the 'limma' package. The protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) and was visualized by Cytoscape. Perilipin2 was a hub gene using the cytoHubba plug-in from Cytoscape. Gene ontology (GO) analysis revealed that the 126 overlapping DEGs were mainly enriched in 'oxidation reduction' [biological process, (BP)], metal ion binding' [molecular function, (MF)] and 'extracellular region' [cellular component, (CC)]. KEGG pathway analysis revealed that perilipin2 was mainly involved in 'PPAR signaling pathway'. DN inhibited perilipin2 expression and PPARγ expression, as by both in vitro and in vivo studies. In vitro experiments demonstrated that perilipin2 inhibition could not only reduced PPARγ expression in podocytes, it could also promote the apoptosis, and inhibit the viability in HG treated podocytes using western blot, CCK8 and flow cytometry assays. Perilipin2 overexpression reversed the effects of HG on inhibiting podocalyxin, nephrin, precursor (pro)-caspase-3/-9 and PPARγ protein expression and increasing cleaved caspase-3/-9 protein expression. Furthermore, the functions of perilipin2 overexpression reversing HG-induced podocyte apoptosis were inhibited by PPARγ inhibitor. In conclusion, the functions of DN-induced podocyte apoptosis were inhibited by activation of the PPARγ signaling pathway caused by perilipin2 overexpression.

中文翻译：

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Perilipin2通过激活PPARγ信号通路抑制糖尿病性肾病引起的足细胞凋亡。

足细胞凋亡在糖尿病性肾病（DN）的发病机理中起关键作用。这项研究的主要目的是研究periplipin2对高糖（HG）诱导的足细胞凋亡及其相关机制的影响。从GSE106841数据集中获得了BTBR ob / ob小鼠与非糖尿病小鼠肾脏中的差异表达基因（DEG），并使用“ limma”软件包进行了选择。蛋白质-蛋白质相互作用（PPI）网络是使用检索相互作用基因的搜索工具（STRING）构建的，并通过Cytoscape可视化。Perilipin2是使用Cytoscape的cytoHubba插件的枢纽基因。基因本体论（GO）分析显示126个重叠的DEG主要富集于“氧化还原” [生物过程（BP）]，金属离子结合” [分子功能（MF）]和“ 细胞外区域的[细胞成分，（CC）]。KEGG通路分析显示，periplipin2主要参与“ PPAR信号通路”。正如体外和体内研究一样，DN抑制periplipin2表达和PPARγ表达。体外实验表明，使用western blot，CCK8和流式细胞术检测，periplipin2抑制不仅可以降低足细胞中PPARγ的表达，还可以促进细胞凋亡，并抑制HG处理的足细胞的生存能力。Perilipin2的过表达逆转了HG抑制podocalyxin，nephrin，前体（pro）-caspase-3 / -9和PPARγ蛋白表达并增加裂解的caspase-3 / -9蛋白表达的作用。此外，PPARγ抑制剂抑制periplipin2过表达逆转HG诱导的足细胞凋亡的功能。结论，