College of Pharmacy, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian, China.
Key Laboratory for Basic and Applied Research on Pharmacodynamic Substances of Traditional Chinese Medicine of Liaoning Province, Dalian Medical University, Dalian, China.
Oxid Med Cell Longev. 2020 Aug 18;2020:9481841. doi: 10.1155/2020/9481841. eCollection 2020.
Clinical application of doxorubicin (Dox) is limited due to its serious side effects including nephrotoxicity, and kidney podocytes play important roles in renal diseases. MicroRNAs (miRNAs) are critical regulators associated with human diseases. The purpose of this study was to explore a novel target in adjusting Dox-induced renal podocyte injury. Through a double luciferase reporter gene experiment, it was found that miR-874-3p directly targeted methionine sulfoxide reductase B3 (MsrB3). During the tests of miR-874-3p inhibitor and MsrB3 siRNA in human podocytes or miR-874-3p antagomir in mice, we found that the expression levels of downstream oxidative stress and apoptosis-related proteins were regulated by miR-874-3p/MsrB3 signal to alleviate or aggravate renal podocyte injury. The data in the present work showed that miR-874-3p aggravated Dox-caused renal podocyte injury by promoting apoptosis and oxidative damage via inhibiting MsrB3. Therefore, miR-874-3p/MsrB3 should be considered as a new therapeutic target in controlling renal podocyte injury induced by Dox.
阿霉素（Dox）的临床应用受到限制，因为其严重的副作用包括肾毒性，而肾脏足细胞在肾脏疾病中起着重要作用。微小 RNA（miRNA）是与人类疾病相关的关键调节因子。本研究旨在探索一种调节 Dox 诱导的肾足细胞损伤的新靶点。通过双荧光素酶报告基因实验，发现 miR-874-3p 可直接靶向甲硫氨酸亚砜还原酶 B3（MsrB3）。在人足细胞中进行 miR-874-3p 抑制剂和 MsrB3 siRNA 测试，或在小鼠中进行 miR-874-3p 拮抗物测试时，我们发现下游氧化应激和细胞凋亡相关蛋白的表达水平通过 miR-874-3p/MsrB3 信号调节，以减轻或加重肾足细胞损伤。本工作中的数据表明，miR-874-3p 通过抑制 MsrB3 促进细胞凋亡和氧化损伤，从而加重 Dox 引起的肾足细胞损伤。因此，miR-874-3p/MsrB3 可被视为控制 Dox 诱导的肾足细胞损伤的新治疗靶点。
