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由miR-145-5p调节的PDZK1通过向线粒体功能来保护内皮细胞亡和糖尿病视网膜病变

Meixia An¹, Jialuo Huang², Jian Zhao¹

¹Department of Ophthalmology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, China.

Experimental eye research

|February 28, 2025

概括

含有PDZ域1 (PDZK1) 缺陷的PDZ域通过损害内皮线粒体功能和促进亡,使糖尿病视网膜病变 (DR) 恶化. 恢复PDZK1可能为DR提供新的治疗策略.

科学领域:

生物医学研究生物医学研究
眼科医生眼科眼科
线粒体生物学线粒体生物学

背景情况:

线粒体在亡和糖尿病视网膜病变 (DR) 中发挥着至关重要的作用.
在DR中,线粒体功能障碍和内皮功能障碍之间的联系机制尚未完全理解.
含有1 (PDZK1) 的PDZ域被调查为潜在的关键因素.

研究的目的:

阐明PDZK1在内皮线粒体功能障碍和DR进展期间的亡中的作用.
确定PDZK1在DR中的功能背后的分子机制.
探索DR的潜在治疗点.

主要方法:

使用了来自DR患者的人类视网膜毛细体内皮细胞 (HRCEC) 和血清.
在高葡萄糖条件下研究PDZK1表达.
进行了PDZK1淘汰赛研究.
分析了线粒体功能,DNA含量和反应性氧物种 (ROS) 生产.
进行了mRNA测序和miRNA分析.

主要成果:

在DR患者和高葡萄糖条件下,PDZK1的下调.
通过诱导内皮细胞亡和线粒体功能障碍,PDZK1淘汰会加剧DR.
缺少PDZK1增加了ATF4表达,并被miR-145-5p抑制.
在DR中,miR-145-5p被上调,导致内皮功能障碍.

结论:

在DR中,PDZK1缺乏对调解视网膜内皮细胞亡和线粒体功能障碍至关重要.
通过miR-145-5p调节PDZK1及其对ATF4的下游影响突出了DR中的新途径.
PDZK1调制为DR治疗提供了一个潜在的治疗策略.

关键词:

糖尿病视网膜病变 - 糖尿病视网膜病变线粒体功能线粒体功能在PDZK1中.

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