Abstract：
Acute kidney injury (AKI) signifies a sudden and prolonged decline in kidney function characterized by tubular cell death and interstitial inflammation. Small nucleolar RNAs (snoRNAs) play pivotal roles in oxidative stress and inflammation, and may play an important role in the AKI process, which remains elusive. an elevated expression of Snord3a is revealed in renal tubules in response to AKI and demonstrates that Snord3a deficiency alleviates renal injury in AKI mouse models. Notably, the deficiency of Snord3a exhibits a mitigating effect on the stimulator of interferon genes (STING)-associated ferroptosis phenotypes and the progression of tubular injury. Mechanistically, Snord3a is shown to regulate the STING signaling axis via promoting STING gene transcription; administration of Snord3a antisense oligonucleotides establishes a significant therapeutic advantage in AKI mouse models. Together, the findings elucidate the transcription regulation mechanism of STING and the crucial roles of the Snord3a-STING axis in ferroptosis during AKI, underscoring Snord3a as a potential prognostic and therapeutic target for AKI.
摘要：
急性肾损伤(AKI)表示以肾小管细胞死亡和间质炎症为特征的肾功能的突然和长期下降。小核仁RNA（snoRNAs）在氧化应激和炎症中起关键作用，并可能在AKI过程中发挥重要作用，这仍然难以捉摸。在对AKI的反应中，肾小管中Snord3a的表达升高，这表明Snord3a缺乏减轻了AKI小鼠模型中的肾损伤。值得注意的是,Snord3a的缺乏对干扰素基因（STING）相关的铁死亡表型的刺激因子和肾小管损伤的进展具有缓解作用。机械上,Snord3a显示通过促进STING基因转录来调节STING信号轴;Snord3a反义寡核苷酸的施用在AKI小鼠模型中建立了显著的治疗优势。一起,这些发现阐明了STING的转录调控机制以及Snord3a-STING轴在AKI过程中铁死亡的关键作用，强调Snord3a是AKI的潜在预后和治疗靶点。
