溶酶体相关蛋白跨膜 5、肾小管衰老和慢性肾功能衰竭的进展。

IF 10.3 1区医学 Q1 UROLOGY & NEPHROLOGY

Journal of The American Society of Nephrology Pub Date : 2024-07-30 DOI:10.1681/ASN.0000000000000446

Xiaohan Liu, Ping Zhan, Yang Zhang, Huiying Jin, Youzhao Wang, Yujie Yang, Ziying Wang, Xiaojie Wang, Qianqian Xu, Junhui Zhen, Rong Sun, Jinpeng Sun, Min Liu, Fan Yi

引用次数: 0

摘要

背景：肾小管衰老是慢性肾脏病（CKD）的一个主要决定因素，确定参与衰老的肾小管上皮细胞的潜在治疗靶点具有重要的临床意义。溶酶体相关跨膜蛋白5（LAPTM5）是一种与T细胞和B细胞受体表达及炎症相关的关键分子。然而，LAPTM5在肾脏中的表达模式以及LAPTM5对CKD发展的贡献仍不清楚：方法：通过建立不同的实验性小鼠 CKD 模型，使用 LAPTM5-/- 小鼠和肾小管特异性 LAPTM5 基因敲除小鼠来研究 LAPTM5 在肾小管衰老中的作用：结果：LAPTM5在马兜铃酸肾病、双侧缺血再灌注损伤（IRI）诱导的CKD或单侧输尿管梗阻（UUO）小鼠的肾脏，尤其是近端肾小管和远端曲小管中表达明显诱导。肾小管特异性缺失 LAPTM5 可抑制肾小管上皮细胞的衰老，缓解老龄小鼠肾小管间质纤维化。此外，缺乏 LAPTM5 可改善慢性肾功能衰竭小鼠的肾损伤和肾小管衰老。从机理上讲，LAPTM5通过介导WWP2溶酶体降解来抑制NICD1的泛素化，进而导致肾小管上皮细胞衰老。值得注意的是，我们还观察到 LAPTM5 在慢性肾功能衰竭患者的肾小管中表达较高，并且 LAPTM5 的水平与慢性肾功能衰竭患者的肾脏纤维化和肾小管衰老相关：结论：LAPTM5通过调节WWP2/NICD1信号通路促进肾小管衰老，并在CKD进展过程中加剧肾损伤。

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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Lysosomal-Associated Protein Transmembrane 5, Tubular Senescence, and Progression of CKD.

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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.