Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Sep 15, 2024; 15(9): 1979-2001
Published online Sep 15, 2024. doi: 10.4239/wjd.v15.i9.1979
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
Yue-Ying Wang, Ke Li, Jia-Jun Wang, Wei Hua, Qi Liu, Yu-Lan Sun, Ji-Ping Qi, Yue-Jia Song
Yue-Ying Wang, Ke Li, Jia-Jun Wang, Wei Hua, Qi Liu, Yu-Lan Sun, Ji-Ping Qi, Department of Pathology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China
Yue-Jia Song, Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China
Co-corresponding authors: Ji-Ping Qi and Yue-Jia Song.
Author contributions: Qi JP and Song YJ designed the study and wrote the first draft of the manuscript; Wang YY, Li K, Wang JJ, Hua W, Liu Q, and Sun YL extracted and analyzed the data. All authors revised the manuscript and read and approved the final version of the submitted manuscript. Qi JP and Song YJ were designated as co-corresponding authors of this study to honor the following responsibilities they shared in: (1) Ensuring accuracy and completeness of the study; (2) Monitoring substantial contributions of all authors; and (3) Maintaining close contact with the editorial board and the publisher during the manuscript submission, revision, and final publication process.
Supported by the National Natural Science Foundation of China, No. 81900743; and Heilongjiang Province Outstanding Young Medical Talents Training Grant Project, China, No. HYD2020YQ0007.
Institutional animal care and use committee statement: All animal experiments were conducted following the national guidelines and the relevant national laws on the protection of animals and were approved by Institutional Animal Care and Use Committee of Harbin Medical University (Approval No. 2022016).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Technical appendix, statistical code, and dataset available by request (songyuejia@hrbmu.edu.cn).
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yue-Jia Song, MD, Professor, Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Nangang District, Harbin 150001, Heilongjiang Province, China. songyuejia@126.com
Received: May 29, 2024
Revised: June 29, 2024
Accepted: July 23, 2024
Published online: September 15, 2024
Processing time: 90 Days and 3.5 Hours
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.

Keywords: Bone marrow mesenchymal stem cells; Exosome; Diabetic cerebral hemorrhage; Neuroinflammation; MicroRNA-129-5p; High mobility group box 1

Core Tip: Diabetic intracerebral hemorrhage is a serious complication of diabetes. In this study, we investigated the effect of exosomes derived from bone marrow-derived mesenchymal stem cells on the attenuation of neuroinflammation and neurological impairment after comorbid cerebral hemorrhage and diabetes. We also explored the specific mechanisms through which they perform their functions. Overall, we hypothesized that bone marrow-derived mesenchymal stem cell exosomes could afford a novel remedy in the treatment of cerebral hemorrhage in patients with diabetes.