Department of Nephrology, The Third Clinical College of Wenzhou Medical University, Wenzhou People's Hospital, Wenzhou, Zhejiang Province, China.
Eur Rev Med Pharmacol Sci. 2019 Feb;23(3):1248-1256. doi: 10.26355/eurrev_201902_17018.
Diabetic nephropathy (DN) is a major diabetic micro-vascular complication, and podocyte apoptosis induced by high glucose (HG) is a typical early feature of DN. Studies have shown that microRNAs (miRNAs) play a crucial role in the pathogenesis of DN. The purpose of the current study was to explore the role and molecular mechanism of miR-770-5p in podocyte apoptosis in DN.
In vitro podocyte model of DN was conducted by treatment conditionally immortalized mouse podocytes with HG (30 mM D-glucose). The level of miR-770-5p in podocytes was detected using quantitative real-time PCR (qRT-PCR), and protein levels were measured using Western blot assay in our current study. The relationship between miR-770-5p and TP53 regulated inhibitor of apoptosis 1 (TRIAP1) was revealed by TargetScan and dual luciferase reporter assay. Cell proliferation ability and cell apoptosis were determined by using cell counting kit-8 (CCK-8) assay and flow cytometer (FCM), respectively.
We found that miR-770-5p was significantly upregulated in podocytes under HG condition. TRIAP1 was a target gene of miR-770-5p and it was down-regulated in podocytes by HG treatment. Further analysis indicated that HG induced cell proliferation ability reduction, cell apoptosis enhancement and apoptotic peptidase activating factor 1(APAF1)/Caspase9 pathway exaltation in podocytes were prevented by miR-770-5p down-regulation. More importantly, the results showed that all the effects of miR-770-5p inhibitor on HG induced podocytes were eliminated by TRIAP1 silencing. S.-Z. Zhang, X.-J. Qiu, S.-S. Dong, L.-N. Zhou, Y. Zhu, M.-D. Wang, L.-W. Jin We showed that miR-770-5p was upregulated in the in vitro model of DN, and it might promote the development of DN through regulating podocyte apoptosis by targeting TRIAP1.
糖尿病肾病（DN）是一种主要的糖尿病微血管并发症，高糖（HG）诱导的足细胞凋亡是 DN 的一个典型早期特征。研究表明，微小 RNA（miRNA）在 DN 的发病机制中起着至关重要的作用。本研究旨在探讨 miR-770-5p 在 DN 中诱导足细胞凋亡中的作用及分子机制。
通过用 HG（30mM D-葡萄糖）处理条件永生化的小鼠足细胞，建立体外 DN 足细胞模型。本研究中通过实时定量 PCR（qRT-PCR）检测 miR-770-5p 在足细胞中的水平，并通过 Western blot 检测蛋白水平。通过 TargetScan 和双荧光素酶报告基因检测揭示 miR-770-5p 与 TP53 调节的凋亡抑制剂 1（TRIAP1）之间的关系。通过细胞计数试剂盒-8（CCK-8）检测和流式细胞仪（FCM）分别测定细胞增殖能力和细胞凋亡。
我们发现 HG 条件下足细胞中 miR-770-5p 显著上调。TRIAP1 是 miR-770-5p 的靶基因，HG 处理下调了足细胞中的 TRIAP1。进一步分析表明，HG 诱导的足细胞增殖能力降低、细胞凋亡增强以及凋亡蛋白酶激活因子 1（APAF1）/Caspase9 通路激活在 miR-770-5p 下调后得到了预防。更重要的是，结果表明 miR-770-5p 抑制剂对 HG 诱导的足细胞的所有作用都被 TRIAP1 沉默所消除。张思臻、邱晓静、董姗姗、周凌云、朱艳、王美东、金亮我们表明，miR-770-5p 在体外 DN 模型中上调，通过靶向 TRIAP1 调节足细胞凋亡，可能促进 DN 的发展。
