脂肪源性间充质干细胞中血栓调节蛋白的过度表达可降低血栓形成风险并提高治疗效果。

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.0000000810

Yoshiki Tanaka, Ayumu Nakashima, Naoki Ishiuchi, Kisho Miyasako, Keisuke Morimoto, Maria Yoshida, Kensuke Sasaki, Satoshi Maeda, Go Matsuda, Takao Masaki

引用次数: 0

摘要

背景：脂肪源性间充质干细胞（ASCs）有望成为器官损伤的新疗法；然而，据报道它们具有促凝活性，这引起了人们对血栓形成风险的担忧。凝血调节蛋白通过与凝血酶结合而发挥抗凝血因子的作用，这就提出了过表达凝血调节蛋白的ASCs （TM-ASCs）可以通过降低血栓栓塞的风险而安全地用于细胞治疗的假设。方法：采用携带血栓调节蛋白cDNA的腺相关病毒制备TM-ASCs。为了研究asc诱导的肾梗死的风险，我们通过肾动脉给药asc给药于单侧缺血再灌注损伤（IRI）和对侧肾切除术的大鼠。为了评估asc诱导肺栓塞的风险，通过尾静脉注射asc给大鼠。此外，我们检测了TM-ASCs是否能有效抑制IRI大鼠的炎症细胞浸润和肾纤维化。此外，我们探索了可增强ASCs中血栓调节蛋白表达的合成化合物。结果：使用腺相关病毒过度表达血栓调节蛋白可降低ASCs所致肾梗死和肺栓塞大鼠的死亡。TM-ASCs对IRI大鼠肾脏炎症和纤维化有明显的缓解作用。TM-ASCs的治疗机制涉及前列腺素E2 （PGE2）分泌增加、体外巨噬细胞表型向免疫抑制型M2转变以及体内损伤区域强效M2巨噬细胞极化。我们用选择性抑制性kappa-B激酶-β (IKKβ)抑制剂预处理获得了血栓调节蛋白表达增强的ASCs。与由腺相关病毒产生的TM-ASCs类似，这些ASCs还能改善血栓性死亡率，显著减轻IRI诱导的肾纤维化。IKKβ抑制剂增强血栓调节蛋白表达的ASCs也增加了PGE2的分泌，导致M2巨噬细胞极化更加明显。结论：血栓调节蛋白表达增强的ASCs消除了血栓形成的风险，增强了治疗效果。

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 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.