多囊肾中的 P2Y2R 和囊肿生长

IF 10.3 1区医学 Q1 UROLOGY & NEPHROLOGY

Journal of The American Society of Nephrology Pub Date : 2024-10-01 Epub Date: 2024-06-07 DOI:10.1681/ASN.0000000000000416

Andre Kraus, Kathrin Skoczynski, Martin Brötsch, Nicolai Burzlaff, Jens Leipziger, Mario Schiffer, Maike Büttner-Herold, Bjoern Buchholz

引用次数: 0

摘要

背景：常染色体显性多囊肾病（ADPKD）的特征是双侧多发性肾囊肿逐渐增大，导致肾功能下降。囊肿的生长主要由离子通道 TMEM16A 介导的 ATP 依赖性氯化物分泌驱动。在疾病晚期，缺氧和缺氧诱导因子（HIF）1α的激活进一步增强了这一途径。ATP导致TMEM16A活化的机制以及HIF-1α如何促进囊肿在体内生长的机制仍未确定：方法：将诱导性小管特异性缺失 Pkd1 的小鼠与同时缺失嘌呤能受体 P2y2r 的小鼠进行比较。此外，还对动物进行了药理激活 HIF-1α 的挑战，并用嘌呤能信号转导拮抗剂苏拉明治疗 Pkd1 缺失的小鼠。此外，还分析了27名ADPKD患者肾切除样本中P2Y2R、TMEM16A和HIF-1α的表达情况：结果：基因缺失 P2y2r 能明显抑制囊肿在体内的生长。此外，P2y2r 基因缺失还降低了药物激活 HIF-1α 导致的多囊表型恶化。应用苏拉明药物抑制嘌呤能信号传导也抑制了体内囊肿的增大。对27名ADPKD患者的肾脏样本进行分析后发现，P2Y2R在囊肿衬里上皮的管腔部位有显著表达：结论：P2Y2R在人和小鼠的多囊肾中明显表达。在 ADPKD 小鼠模型中，P2Y2R 的缺失和拮抗可减少囊肿增大。

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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P2Y2R and Cyst Growth in Polycystic Kidney Disease.

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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.