Bone marrow-derived mesenchymal stem cell-derived exosome-loaded miR-129-5p targets high-mobility group box 1 attenuates neurological-impairment after diabetic cerebral hemorrhage.

IF 4.2 3区医学 Q1 ENDOCRINOLOGY & METABOLISM

World Journal of Diabetes Pub Date : 2024-09-15 DOI:10.4239/wjd.v15.i9.1979

Yue-Ying Wang, Ke Li, Jia-Jun Wang, Wei Hua, Qi Liu, Yu-Lan Sun, Ji-Ping Qi, Yue-Jia Song

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Abstract

Background: Diabetic intracerebral hemorrhage (ICH) is a serious complication of diabetes. The role and mechanism of bone marrow mesenchymal stem cell (BMSC)-derived exosomes (BMSC-exo) in neuroinflammation post-ICH in patients with diabetes are unknown. In this study, we investigated the regulation of BMSC-exo on hyperglycemia-induced neuroinflammation.

Aim: To study the mechanism of BMSC-exo on nerve function damage after diabetes complicated with cerebral hemorrhage.

Methods: BMSC-exo were isolated from mouse BMSC media. This was followed by transfection with microRNA-129-5p (miR-129-5p). BMSC-exo or miR-129-5p-overexpressing BMSC-exo were intravitreally injected into a diabetes mouse model with ICH for in vivo analyses and were cocultured with high glucose-affected BV2 cells for in vitro analyses. The dual luciferase test and RNA immunoprecipitation test verified the targeted binding relationship between miR-129-5p and high-mobility group box 1 (HMGB1). Quantitative polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay were conducted to assess the levels of some inflammation factors, such as HMGB1, interleukin 6, interleukin 1β, toll-like receptor 4, and tumor necrosis factor α. Brain water content, neural function deficit score, and Evans blue were used to measure the neural function of mice.

Results: Our findings indicated that BMSC-exo can promote neuroinflammation and functional recovery. MicroRNA chip analysis of BMSC-exo identified miR-129-5p as the specific microRNA with a protective role in neuroinflammation. Overexpression of miR-129-5p in BMSC-exo reduced the inflammatory response and neurological impairment in comorbid diabetes and ICH cases. Furthermore, we found that miR-129-5p had a targeted binding relationship with HMGB1 mRNA.

Conclusion: We demonstrated that BMSC-exo can reduce the inflammatory response after ICH with diabetes, thereby improving the neurological function of the brain.

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骨髓间充质干细胞外泌体加载的miR-129-5p靶向高移动组盒1，可减轻糖尿病脑出血后的神经损伤。

背景：糖尿病脑出血（ICH）是糖尿病的一种严重并发症。骨髓间充质干细胞（BMSC）衍生的外泌体（BMSC-exo）在糖尿病患者 ICH 后神经炎症中的作用和机制尚不清楚。目的：研究BMSC-exo对糖尿病并发脑出血后神经功能损伤的机制：方法：从小鼠BMSC培养基中分离出BMSC-exo。方法：从小鼠 BMSC 培养基中分离出 BMSC-exo，然后转染 microRNA-129-5p （miR-129-5p）。将 BMSC-exo 或过表达 miR-129-5p 的 BMSC-exo 经静脉注射到糖尿病小鼠 ICH 模型中进行体内分析，并与受高糖影响的 BV2 细胞共培养进行体外分析。双重荧光素酶试验和 RNA 免疫沉淀试验验证了 miR-129-5p 与高移动性基团框 1（HMGB1）之间的靶向结合关系。定量聚合酶链式反应、Western 印迹和酶联免疫吸附试验评估了一些炎症因子的水平，如 HMGB1、白细胞介素 6、白细胞介素 1β、toll 样受体 4 和肿瘤坏死因子 α；脑含水量、神经功能缺损评分和伊文思蓝用于测量小鼠的神经功能：结果：我们的研究结果表明，BMSC-exo 能促进神经炎症和功能恢复。对 BMSC-exo 的 MicroRNA 芯片分析发现，miR-129-5p 是对神经炎症具有保护作用的特异性 microRNA。在BMSC-exo中过表达miR-129-5p可减轻合并糖尿病和ICH病例的炎症反应和神经功能损伤。此外，我们还发现 miR-129-5p 与 HMGB1 mRNA 存在靶向结合关系：结论：我们证明了 BMSC-exo 能减轻糖尿病合并 ICH 后的炎症反应，从而改善大脑神经功能。

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来源期刊

World Journal of Diabetes ENDOCRINOLOGY & METABOLISM-

自引率

2.40%

发文量

909

期刊介绍： The WJD is a high-quality, peer reviewed, open-access journal. The primary task of WJD is to rapidly publish high-quality original articles, reviews, editorials, and case reports in the field of diabetes. In order to promote productive academic communication, the peer review process for the WJD is transparent; to this end, all published manuscripts are accompanied by the anonymized reviewers’ comments as well as the authors’ responses. The primary aims of the WJD are to improve diagnostic, therapeutic and preventive modalities and the skills of clinicians and to guide clinical practice in diabetes. Scope: Diabetes Complications, Experimental Diabetes Mellitus, Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus, Diabetes, Gestational, Diabetic Angiopathies, Diabetic Cardiomyopathies, Diabetic Coma, Diabetic Ketoacidosis, Diabetic Nephropathies, Diabetic Neuropathies, Donohue Syndrome, Fetal Macrosomia, and Prediabetic State.