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

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

机构地区：[1]Department of Pathology,The First Affiliated Hospital of Harbin Medical University,Harbin 150001,Heilongjiang Province,China [2]Department of Endocrinology,The First Affiliated Hospital of Harbin Medical University,Harbin 150001,Heilongjiang Province,China

出　　处：《World Journal of Diabetes》2024年第9期1979-2001,共23页世界糖尿病杂志（英文版）（电子版）

基　　金：Supported by the National Natural Science Foundation of China,No.81900743;Heilongjiang Province Outstanding Young Medical Talents Training Grant Project,China,No.HYD2020YQ0007.

摘　　要：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-129-5poverexpressing BMSC-exo were intravitreally injected into a diabetes mouse model with ICH for in vivo analyses and were cocultured with high glucoseaffected 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 factorα.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.

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

分 类 号：R587.2[医药卫生—内分泌]