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细胞外线粒体衍生的囊泡通过调节氧化应激和线粒体功能障碍,影响糖尿病足的进展

Huihui Zhang^1,2, Zi Yan^2,3,4, Junyou Zhu⁵

¹Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

|January 21, 2025

概括

线粒体衍生囊泡 (MDVs) 会增加糖尿病足 (DFU) 的发生,并通过破坏细胞线粒体,损害伤口愈合. 抑制排序Nexin 9 (SNX9) 挽救了这种效应,建议MDV作为DFU的治疗标.

科学领域:

生物医学研究生物医学研究
糖尿病并发症糖尿病并发症
细胞外囊泡生物学细胞外囊泡生物学

背景情况:

糖尿病足 (DFU) 是一种严重的糖尿病并发症,病因不明.
细胞外囊泡 (EVs) 在DFU病原发生中的参与正在调查中.
线粒体衍生囊泡 (MDVs) 在DFU中被确定为潜在的显著EVs.

研究的目的:

调查MDV在DFU中的作用.
在DFU中确定MDV的监管机制.
评估MDV作为DFU治疗的治疗目标.

主要方法:

纳米流细胞测量用于检测DFU皮肤组织中的EV.
对单细胞数据集的分析,以确定MDV监管者.
在高葡萄糖条件下使用纤维细胞衍生MDV的体外研究.
在糖尿病小鼠模型中的体内实验.

主要成果:

在DFU组织中,外线粒体膜20 (TOM20) + MDVs的转位酶显著增加.
排序Nexin 9 (SNX9) 被确定为MDV增加的潜在调节者.
在体外MDV模仿DFU组织MDV,促进细胞亡,氧化应激和线粒体功能障碍.
在体内,MDVs在糖尿病小鼠中损害了伤口愈合,这种效果被SNX9抑制剂逆转.

结论:

在DFU中,MDVs通过诱导线粒体功能障碍和损害伤口愈合来发挥有害作用.
在DFU中,SNX9调节了MDV相关的病理.
针对MDVs为DFU提供了一个有前途的治疗策略.

关键词:

糖尿病人的足部.细胞外囊泡中的细胞外囊泡.线粒体中的线粒体.线粒体衍生的囊泡.氧化应激是一种氧化应激.

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