Xu Mingzhu, Yi Mengqiu, Li Na
Department of Nephrology, China-Japan Union Hospital of Jilin University, Jilin, China.
Intensive Care Unit, Songyuan Jilin Oilfield Hospital, Jilin, China.
Environ Toxicol. 2021 Jul;36(7):1402-1411. doi: 10.1002/tox.23136. Epub 2021 Apr 9.
Glomerulonephritis, also known as nephritis syndrome (nephritis for short), is a common kidney disease. Previous research has proved that microRNAs (miRNAs) frequently regulate various diseases including nephritis. Nonetheless, the biological function and molecular mechanism of miR-17-5p are unclear in nephritis. In the current study, RT-qPCR analysis showed that miR-17-5p was downregulated in Ang II-induced podocytes. Also, according to the results from RT-qPCR analysis, CCK-8 assay, flow cytometric analysis, western blot analysis, and ELISA miR-17-5p elevation alleviated Ang II-induced podocyte injury. Besides, luciferase reporter assay, western blot and RT-qPCR analyses revealed that SMOC2 was targeted by miR-17-5p in Ang II-induced podocytes. Additionally, rescue assays demonstrated that overexpressed SMOC2 counteracted the influence of overexpressed miR-17-5p on cell injury of Ang II-induced podocytes. Moreover, our data suggested that miR-17-5p-SMOC2 axis regulated TGFβ and NF-κB signaling activation in Ang II-induced podocytes. SMOC2 regulated cell viability, apoptosis and extracellular matrix (ECM) deposition in Ang II-induced podocytes via TGFβ signaling, and SMOC2 regulated inflammation in Ang II-induced podocytes through NF-κB signaling. Overall, our study demonstrated that miRNA-17-5p restrained the dysfunction of Ang-II induced podocytes by suppressing SMOC2 via the NF-κB and TGFβ signaling.
肾小球肾炎，也称为肾炎综合征（简称肾炎），是一种常见的肾脏疾病。先前的研究已证明，微小RNA（miRNA）频繁调节包括肾炎在内的各种疾病。尽管如此，miR-17-5p在肾炎中的生物学功能和分子机制仍不清楚。在本研究中，RT-qPCR分析表明，miR-17-5p在血管紧张素II诱导的足细胞中表达下调。此外，根据RT-qPCR分析、CCK-8检测、流式细胞术分析、蛋白质印迹分析和ELISA的结果，miR-17-5p表达升高可减轻血管紧张素II诱导的足细胞损伤。此外，荧光素酶报告基因检测、蛋白质印迹和RT-qPCR分析显示，在血管紧张素II诱导的足细胞中，SMOC2是miR-17-5p的靶标。此外，挽救实验表明，过表达的SMOC2可抵消过表达的miR-17-5p对血管紧张素II诱导的足细胞损伤的影响。此外，我们的数据表明，miR-17-5p-SMOC2轴调节血管紧张素II诱导的足细胞中TGFβ和NF-κB信号的激活。SMOC2通过TGFβ信号调节血管紧张素II诱导的足细胞的细胞活力、凋亡和细胞外基质（ECM）沉积，并且SMOC2通过NF-κB信号调节血管紧张素II诱导的足细胞中的炎症。总体而言，我们的研究表明，miRNA-17-5p通过NF-κB和TGFβ信号抑制SMOC2，从而抑制血管紧张素II诱导的足细胞功能障碍。
