Yan Linjing, Guo Liang
School of Exercise and Health and Shanghai Frontiers Science Research Base of Exercise and Metabolic Health, Shanghai University of Sport, Shanghai 200438, PR China.
School of Exercise and Health and Shanghai Frontiers Science Research Base of Exercise and Metabolic Health, Shanghai University of Sport, Shanghai 200438, PR China.
Life Sci. 2025 Feb 15;363:123355. doi: 10.1016/j.lfs.2024.123355. Epub 2025 Jan 6.
Diabetic nephropathy (DN) is one of the most common microvascular complications of diabetes mellitus, characterized by progressive deterioration of renal structure and function, which may eventually lead to end-stage kidney disease (ESKD). The N6-methyladenosine (m6A) methylation, an important modality of RNA modification, involves three classes of key regulators, writers (e.g., METTL3), erasers (e.g., FTO, ALKBH5) and readers (e.g., YTHDF2), which play important roles in DN. Writers are responsible for introducing m6A modifications on RNAs, erasers remove m6A modifications and readers recognize and bind m6A-modified RNAs to regulate RNAs functions, such as mRNA stability, translation and localization. In DN, abnormal m6A modification may promote kidney injury and proteinuria by regulating key pathways involved in multiple processes, including lipid metabolism and inflammatory response, in kidney cells such as podocytes. Therefore, an in-depth study of the role and mechanism of m6A methylation that are regulated by "writers", "erasers" and "readers" in DN is expected to provide new targets and strategies for the prevention and treatment of DN.
糖尿病肾病（DN）是糖尿病最常见的微血管并发症之一，其特征是肾脏结构和功能进行性恶化，最终可能导致终末期肾病（ESKD）。N6-甲基腺苷（m6A）甲基化是RNA修饰的一种重要形式，涉及三类关键调节因子，即“书写器”（如METTL3）、“擦除器”（如FTO、ALKBH5）和“读取器”（如YTHDF2），它们在DN中发挥重要作用。“书写器”负责在RNA上引入m6A修饰，“擦除器”去除m6A修饰，“读取器”识别并结合m6A修饰的RNA以调节RNA功能，如mRNA稳定性、翻译和定位。在DN中，异常的m6A修饰可能通过调节足细胞等肾细胞中多个过程（包括脂质代谢和炎症反应）所涉及的关键途径来促进肾损伤和蛋白尿。因此，深入研究由“书写器”、“擦除器”和“读取器”调节的m6A甲基化在DN中的作用和机制，有望为DN的预防和治疗提供新的靶点和策略。
