Li Bojun, Lin Fangyou, Song Baofeng, Han ShangTing, Ye Zehua, Sun Yushi, Wang Peihan, Xia Yuqi, Yu Weimin, Zhou Xiangjun, Cheng Fan
Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China.
Nat Commun. 2025 Aug 12;16(1):7483. doi: 10.1038/s41467-025-62433-2.
Acute kidney injury (AKI) is a serious clinical condition whose underlying mechanisms remain unclear. Here we identify a long non-coding RNA, RSDR, as a critical regulator of renal protection in AKI. RSDR interacts with the RNA-binding protein hnRNPK, forming a positive feedback loop that enhances the transcription of DHODH, a key ferroptosis-suppressing gene. Mechanistically, RSDR promotes the nuclear retention of hnRNPK and facilitates epigenetic activation of DHODH, thereby limiting ferroptosis in renal tubular epithelial cells. In vivo overexpression of RSDR attenuates ferroptosis and preserves renal function in male mice during AKI. Clinically, urinary RSDR levels are significantly reduced in patients with AKI, and machine learning analysis suggests potential utility in disease detection. These findings highlight RSDR as a central regulator of ferroptosis and provide mechanistic insights into lncRNA-mediated tubular protection in AKI.
急性肾损伤（AKI）是一种严重的临床病症，其潜在机制尚不清楚。在此，我们鉴定出一种长链非编码RNA，即RSDR，它是急性肾损伤中肾脏保护的关键调节因子。RSDR与RNA结合蛋白hnRNPK相互作用，形成一个正反馈环，增强关键的铁死亡抑制基因DHODH的转录。从机制上讲，RSDR促进hnRNPK在细胞核内的保留，并促进DHODH的表观遗传激活，从而限制肾小管上皮细胞中的铁死亡。在体内过表达RSDR可减轻铁死亡，并在雄性小鼠急性肾损伤期间保护肾功能。临床上，急性肾损伤患者的尿RSDR水平显著降低，机器学习分析表明其在疾病检测中具有潜在用途。这些发现突出了RSDR作为铁死亡的核心调节因子，并为急性肾损伤中lncRNA介导的肾小管保护提供了机制性见解。
