KRT20抑制急性肾损伤外泌体PRDX2分泌和铁下垂。

IF 9.4 1区医学 Q1 UROLOGY & NEPHROLOGY

Journal of The American Society of Nephrology Pub Date : 2025-07-25 DOI:10.1681/ASN.0000000805

Lijun Yin, Zebin Deng, Jiachen Liu, Lin Ye, Jun Huang, Yingbo Dai, Yinhuai Wang, Yu Li, Xuejing Zhu, Yu Lu, Yong Wu, Baiyu Feng, Yunhui He, Dongshan Zhang, Shaobin Duan, Zheng Dong, Fei Deng, Anqun Chen

引用次数: 0

摘要

背景：急性肾损伤（AKI）是临床上常见的肾功能不全综合征。角蛋白20 （Keratin 20, KRT20）是一种中间纤维成分，被广泛认为是肾小管损伤的生物标志物，但其在肾脏疾病中的确切功能尚不清楚。方法：分析小鼠缺血/再灌注诱导AKI模型的RNA测序数据，以评估KRT20转录物水平。随后在两种不同的AKI小鼠模型中检测了特异性Krt20敲除对肾近端小管细胞（Krt20PTKO）的影响。荧光素酶报告基因检测和ChIP-PCR鉴定KRT20表达调控的转录因子，免疫沉淀质谱法鉴定KRT20的下游靶点。此外，评估KRT20和过氧化物还蛋白2 （PRDX2）在急性肾小管坏死患者中的临床意义。结果：肾近端小管细胞KRT20在AKI早期显著上调，先于KIM1表达的诱导。在缺血/再灌注和顺铂诱导的AKI模型中，Fosb介导了这种上调。肾近端小管细胞特异性敲除Krt20加重了AKI期间的肾损伤。在机制上，KRT20通过隔离PRDX2（一种抗氧化蛋白）和抑制PRDX2的外泌体分泌来预防AKI，最终防止肾小管细胞铁凋亡。进一步分析发现，alg -2相互作用蛋白X （Alix）促进PRDX2外泌体释放，而KRT20与Alix竞争结合PRDX2的n端结构域，从而将PRDX2保留在细胞内。最后，临床样本中KRT20和PRDX2的表达水平与肾损伤严重程度和肾功能下降相关。结论：这些研究结果表明，KRT20在AKI的早期阶段上调，通过隔离PRDX2和抑制铁凋亡来保护肾小管细胞。

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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Keratin 20 Suppresses Exosomal Secretion of Peroxiredoxin 2 and Ferroptosis in Acute Kidney Injury.

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来源期刊

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.