Zhang Yu, Zuo Xiangrong
Department of Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China.
Department of Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, No.300 GuangZhou Road, Nanjing, Jiangsu, People’s Republic of China.
Open Life Sci. 2021 Dec 31;16(1):1393-1404. doi: 10.1515/biol-2021-0127. eCollection 2021.
Renal ischemia-reperfusion injury (IRI) is one of the main causes of acute kidney injury (AKI). So far, there have been many studies on renal IRI, although an effective treatment method has not been developed. In recent years, growing evidence has shown that small noncoding RNAs play an important regulatory role in renal IRI. This article aims to explore whether microRNA-25-3p (miR-25-3p) plays a role in the molecular mechanism of renal IRI. The results showed that the expression level of miR-25-3p was significantly downregulated in a rat renal IRI model, and this result was confirmed with in vitro experiments. After the hypoxia-reoxygenation treatment, the apoptosis level of NRK-52E cells transfected with miR-25-3p mimics decreased significantly, and this antiapoptotic effect was antagonized by miR-25-3p inhibitors. In addition, we confirmed that DKK3 is a target of miR-25-3p. miR-25-3p exerts its protective effect against apoptosis on NRK-52E cells by inhibiting the expression of DKK3, and downregulating the expression level of miR-25-3p could disrupt this protective effect. In addition, we reconfirmed the role of miR-25-3p in rats. Therefore, we confirmed that miR-25-3p may target DKK3 to reduce renal cell damage caused by hypoxia and that miR-25-3p may be a new potential treatment for renal IRI.
肾缺血再灌注损伤（IRI）是急性肾损伤（AKI）的主要原因之一。到目前为止，虽然尚未开发出有效的治疗方法，但对肾IRI已有许多研究。近年来，越来越多的证据表明，小非编码RNA在肾IRI中发挥着重要的调节作用。本文旨在探讨微小RNA-25-3p（miR-25-3p）是否在肾IRI的分子机制中发挥作用。结果表明，在大鼠肾IRI模型中，miR-25-3p的表达水平显著下调，体外实验也证实了这一结果。缺氧复氧处理后，转染miR-25-3p模拟物的NRK-52E细胞凋亡水平显著降低，而这种抗凋亡作用被miR-25-3p抑制剂所拮抗。此外，我们证实DKK3是miR-25-3p的一个靶点。miR-25-3p通过抑制DKK3的表达对NRK-52E细胞的凋亡发挥保护作用，下调miR-25-3p的表达水平会破坏这种保护作用。此外，我们再次证实了miR-25-3p在大鼠中的作用。因此，我们证实miR-25-3p可能靶向DKK3以减少缺氧引起的肾细胞损伤，并且miR-25-3p可能是肾IRI的一种新的潜在治疗方法。
