Róka Beáta, Tod Pál, Kaucsár Tamás, Bukosza Éva Nóra, Vörös Imre, Varga Zoltán V, Petrovich Balázs, Ágg Bence, Ferdinandy Péter, Szénási Gábor, Hamar Péter
Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary.
Institute for Translational Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary.
Biomedicines. 2021 Jul 14;9(7):815. doi: 10.3390/biomedicines9070815.
(1) Background: Ischemia reperfusion (IR) is the leading cause of acute kidney injury (AKI) and results in predisposition to chronic kidney disease. We demonstrated that delayed contralateral nephrectomy (Nx) greatly improved the function of the IR-injured kidney and decelerated fibrosis progression. Our aim was to identify microRNAs (miRNA/miR) involved in this process. (2) Methods: NMRI mice were subjected to 30 min of renal IR and one week later to Nx/sham surgery. The experiments were conducted for 7-28 days after IR. On day 8, multiplex renal miRNA profiling was performed. Expression of nine miRNAs was determined with qPCR at all time points. Based on the target prediction, plexin-A2 and Cd2AP were measured by Western blot. (3) Results: On day 8 after IR, the expression of 20/1195 miRNAs doubled, and 9/13 selected miRNAs were upregulated at all time points. Nx reduced the expression of several ischemia-induced pro-fibrotic miRNAs (fibromirs), such as miR-142a-duplex, miR-146a-5p, miR-199a-duplex, miR-214-3p and miR-223-3p, in the injured kidneys at various time points. Plexin-A2 was upregulated by IR on day 10, while Cd2AP was unchanged. (4) Conclusion: Nx delayed fibrosis progression and decreased the expression of ischemia-induced fibromirs. The protein expression of plexin-A2 and Cd2AP is mainly regulated by factors other than miRNAs.
（1）背景：缺血再灌注（IR）是急性肾损伤（AKI）的主要原因，并导致慢性肾脏病的易感性增加。我们证明，延迟对侧肾切除术（Nx）可显著改善IR损伤肾脏的功能，并减缓纤维化进程。我们的目的是鉴定参与此过程的微小RNA（miRNA/miR）。（2）方法：将NMRI小鼠进行30分钟的肾脏IR，一周后进行Nx/假手术。在IR后7 - 28天进行实验。在第8天，进行多重肾脏miRNA分析。在所有时间点用qPCR测定9种miRNA的表达。基于靶标预测，通过蛋白质印迹法检测丛状蛋白A2和Cd2AP。（3）结果：IR后第8天，20/1195种miRNA的表达增加了一倍，并且在所有时间点9/13种选定的miRNA上调。Nx在不同时间点降低了损伤肾脏中几种缺血诱导的促纤维化miRNA（纤维化miRNA）的表达，如miR-142a双链体、miR-146a-5p、miR-199a双链体、miR-214-3p和miR-223-3p。丛状蛋白A2在第10天被IR上调，而Cd2AP不变。（4）结论：Nx延迟了纤维化进程并降低了缺血诱导的纤维化miRNA的表达。丛状蛋白A2和Cd2AP的蛋白表达主要受miRNA以外的因素调节。
