MSC-derived Exosomal miR-125b-5p Suppressed Retinal Microvascular Endothelial Cell Ferroptosis in Diabetic Retinopathy.

IF 4 2区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

STEM CELLS Pub Date : 2025-04-18 DOI:10.1093/stmcls/sxaf023

Jun Tong, Yueqin Chen, Xinru Ling, Zhenping Huang, Genhong Yao, Zhenggao Xie

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Abstract

Progressive endothelial cell injury of retinal vascular is a vital factor in diabetic retinopathy (DR) pathogenesis. Mesenchymal stem cells-derived small extracellular vesicles (MSC-sEVs) showed beneficial effects on DR. However, the effects of MSC-sEVs in endothelial dysfunction of DR and the mechanism is still unclear. In this study, MSC-sEVs mitigated retinal blood-retina barrier (BRB) impairment in rats with streptozotocin (STZ)-induced DR by reducing ferroptosis in vivo and in vitro. MSC-sEVs miRNA sequencing analysis revealed that miR-125b-5p may mediate human retina microvascular endothelial cells (HRMECs) ferroptosis and P53 as a downstream target based on dual-luciferase reporter assays. Silencing miR-125b-5p in MSC-sEVs reversed the therapeutic effects of MSC-sEVs on rats with DR and advanced glycation end products (AGEs)-treated HRMECs. Additionally, overexpression of miR-125b-5p could diminish ferroptosis in HRMECs, and this effect could be effectively reversed by overexpressing P53. This study indicated the potential therapeutic effect of MSC-sEVs on vascular endothelial function maintenance and that the delivery of sEVs carrying miR-125b-5p could prevent endothelial cell ferroptosis by inhibiting P53, thereby protecting the BRB.

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msc来源的外泌体miR-125b-5p抑制糖尿病视网膜病变视网膜微血管内皮细胞铁下垂。

进行性视网膜血管内皮细胞损伤是糖尿病视网膜病变发病的重要因素。间充质干细胞衍生的小细胞外囊泡（MSC-sEVs）对DR有有益作用，但MSC-sEVs在DR内皮功能障碍中的作用及其机制尚不清楚。在本研究中，msc - sev通过减少体内和体外的铁上吊，减轻了链脲佐菌素（STZ）诱导的DR大鼠视网膜血视网膜屏障（BRB）损伤。MSC-sEVs miRNA测序分析显示，基于双荧光素酶报告基因检测，miR-125b-5p可能介导人视网膜微血管内皮细胞（HRMECs）铁下垂和P53作为下游靶点。在msc - sev中沉默miR-125b-5p逆转了msc - sev对DR和晚期糖基化终产物（AGEs）治疗的hrmec大鼠的治疗作用。此外，过表达miR-125b-5p可以减少HRMECs中的铁下垂，并且这种作用可以通过过表达P53有效逆转。本研究表明msc - sev对血管内皮功能维持的潜在治疗作用，并且携带miR-125b-5p的sev递送可以通过抑制P53来阻止内皮细胞铁下沉，从而保护BRB。

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

STEM CELLS 医学-生物工程与应用微生物

CiteScore

10.30

自引率

1.90%

发文量

104

审稿时长

3 months

期刊介绍： STEM CELLS, a peer reviewed journal published monthly, provides a forum for prompt publication of original investigative papers and concise reviews. STEM CELLS is read and written by clinical and basic scientists whose expertise encompasses the rapidly expanding fields of stem and progenitor cell biology. STEM CELLS covers: Cancer Stem Cells, Embryonic Stem Cells/Induced Pluripotent Stem (iPS) Cells, Regenerative Medicine, Stem Cell Technology: Epigenetics, Genomics, Proteomics, and Metabonomics, Tissue-Specific Stem Cells, Translational and Clinical Research.