人间质干细胞的肾血管疾病和线粒体功能障碍

IF 10.3 1区医学 Q1 UROLOGY & NEPHROLOGY

Journal of The American Society of Nephrology Pub Date : 2024-11-01 Epub Date: 2024-07-16 DOI:10.1681/ASN.0000000000000440

Alfonso Eirin, Sarosh Siddiqi, Autumn G Hughes, Yamei Jiang, Xiang-Yang Zhu, Sara Kazeminia, Bo Lu, Li Xing, Brandon Lu, Hui Tang, Ailing Xue, Amir Lerman, Stephen C Textor, Lilach O Lerman

引用次数: 0

摘要

背景：肾血管疾病会导致肾缺血、高血压和最终的肾衰竭。脂肪组织间充质干/基质细胞（间充质干细胞）的自体移植可改善狭窄肾脏的灌注和氧合，但相关的动脉粥样硬化和高血压可能会削弱间充质干细胞的功效。我们推测，新血管疾病会改变人间叶干细胞转录组，并损害其修复能力：方法：从肾血管疾病患者和健康志愿者（每组 3 人）的皮下腹部脂肪中获取间充质干细胞，对其进行特征描述，然后在肾动脉狭窄或假手术（每组 6 人）2 周后将间充质干细胞（5x10^5/200μL）注射到小鼠体内。两周后，对小鼠进行成像和组织研究。此外，还通过 mRNA/microRNA（miRNA）测序鉴定了健康志愿者和新血管疾病间充质干细胞的特征。在此基础上，对 miRNA 调节前后的间充质干细胞增殖和线粒体损伤进行了体外评估，并对使用 miR-378h 模拟物（n=5）或抑制剂（n=4）预处理的新血管疾病间充质干细胞的肾动脉狭窄小鼠进行了体内评估：结果：间充质干细胞移植到狭窄小鼠肾脏。健康志愿者-间充质干细胞（而非新血管疾病-间充质干细胞）降低了血压，改善了血清肌酐水平和狭窄肾皮质灌注与氧合，并减轻了肾小管周围毛细血管缺失、肾小管损伤和纤维化。新血管疾病间充质干细胞与健康志愿者间充质干细胞相比，上调的基因主要与转录和细胞增殖有关，而下调的基因主要编码线粒体蛋白。上调的 miRNA（包括 miR-378h）主要靶向核编码的线粒体基因，而下调的 miRNA 主要靶向与转录和细胞增殖有关的基因。miR-378h抑制后，间充质干细胞增殖相似，但其线粒体结构和体内外修复功能均得到改善：结论：肾血管疾病损害了人间叶干细胞的修复能力，这可能是通过靶向线粒体基因的 miR-378h 失调造成的。

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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Renovascular Disease and Mitochondrial Dysfunction in Human Mesenchymal Stem Cells.

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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.