RNA-Binding Protein Lgals3 , Ferroptosis, and Acute Kidney Injury.

IF 9.4 1区 医学 Q1 UROLOGY & NEPHROLOGY Journal of The American Society of Nephrology Pub Date : 2025-02-10 DOI:10.1681/ASN.0000000638
Lijia Chen, Zehua Ye, Songyuan Yang, Jinna Xie, Haoyong Li, Xiangjun Zhou, Fan Cheng
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rna结合蛋白Lgals3、铁下垂和急性肾损伤。
背景:急性肾损伤(AKI)是一种以肾功能急剧下降为特征的综合征,对患者的生存构成重大威胁。RNA结合蛋白(RBP)在AKI中的作用尚不清楚,我们发现一种重要的RBP Lgals3可能介导AKI的进展。方法:采用Lgals3-/-小鼠、Nr4a1-/-小鼠、交联免疫沉淀法和高通量测序法检测Lgals3在AKI中的作用及其靶向结合蛋白。结果:在体内和体外AKI模型中,Lgals3的表达明显升高。在体内和体外AKI模型中,抑制Lgals3可减轻肾损伤。相反,Lgals3的肾特异性过表达加重了肾损伤。从机制上讲,Lgals3通过AAUAAA结合到Nr4a1的3'-非翻译区,导致Nr4a1的上调和随后Bap1转录的增强,促进AKI中的铁凋亡。此外,在AKI模型中,敲除Nr4a1或用反义寡核苷酸(ASO)抑制AAUAAA区域可保护小鼠免受lgals3诱导的铁下垂。结论:Lgals3通过AAUAAA与Nr4a1的3'UTR区结合,导致铁下沉激活,从而导致肾损伤。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of The American Society of Nephrology
Journal of The American Society of Nephrology 医学-泌尿学与肾脏学
CiteScore
22.40
自引率
2.90%
发文量
492
审稿时长
3-8 weeks
期刊介绍: The Journal of the American Society of Nephrology (JASN) stands as the preeminent kidney journal globally, offering an exceptional synthesis of cutting-edge basic research, clinical epidemiology, meta-analysis, and relevant editorial content. Representing a comprehensive resource, JASN encompasses clinical research, editorials distilling key findings, perspectives, and timely reviews. Editorials are skillfully crafted to elucidate the essential insights of the parent article, while JASN actively encourages the submission of Letters to the Editor discussing recently published articles. The reviews featured in JASN are consistently erudite and comprehensive, providing thorough coverage of respective fields. Since its inception in July 1990, JASN has been a monthly publication. JASN publishes original research reports and editorial content across a spectrum of basic and clinical science relevant to the broad discipline of nephrology. Topics covered include renal cell biology, developmental biology of the kidney, genetics of kidney disease, cell and transport physiology, hemodynamics and vascular regulation, mechanisms of blood pressure regulation, renal immunology, kidney pathology, pathophysiology of kidney diseases, nephrolithiasis, clinical nephrology (including dialysis and transplantation), and hypertension. Furthermore, articles addressing healthcare policy and care delivery issues relevant to nephrology are warmly welcomed.
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