MiR-4465-modified mesenchymal stem cell-derived small extracellular vesicles inhibit liver fibrosis development via targeting LOXL2 expression  

作　　者：Yanjin WANG Yifei CHEN Fuji YANG Xiaolong YU Ying CHU Jing ZHOU Yongmin YAN Jianbo XI 

机构地区：[1]Department of Laboratory Medicine,Wujin Hospital Affiliated with Jiangsu University,Jiangsu University,Changzhou 213017,China [2]Department of Laboratory Medicine,School of Medicine,Jiangsu University,Zhenjiang 212013,China [3]Changzhou Key Laboratory of Molecular Diagnostics and Precision Cancer Medicine,Wujin Clinical College of Xuzhou Medical University,Changzhou 213017,China

出　　处：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2024年第7期594-604,共11页浙江大学学报（英文版）B辑（生物医学与生物技术）

基　　金：supported by the National Natural Science Foundation of China(No.82272421);the Jiangsu Provincial Key Research and Development Program(No.BE2021690);the Changzhou's 14th Five-year Plan Project to Train Highlevel Health Professionals(No.2022CZLJ027);the Scientific Project of Jiangsu Health Commission(No.Z2020038);the Changzhou Sci&Tech Program(No.CJ20220164),China.

摘　　要：Liver fibrosis is a significant health burden,marked by the consistent deposition of collagen.Unfortunately,the currently available treatment approaches for this condition are far from optimal.Lysyl oxidase-like protein 2(LOXL2)secreted by hepatic stellate cells(HSCs)is a crucial player in the cross-linking of matrix collagen and is a significant target for treating liver fibrosis.Mesenchymal stem cell-derived small extracellular vesicles(MSC-sEVs)have been proposed as a potential treatment option for chronic liver disorders.Previous studies have found that MSC-sEV can be used for microRNA delivery into target cells or tissues.It is currently unclear whether microRNA-4465(miR-4465)can target LOXL2 and inhibit HSC activation.Additionally,it is uncertain whether MSC-sEV can be utilized as a gene therapy vector to carry miR-4465 and effectively inhibit the progression of liver fibrosis.This study explored the effect of miR-4465-modified MSC-sEV(MSC-sEVmiR-4465)on LOXL2 expression and liver fibrosis development.The results showed that miR-4465 can bind specifically to the promoter of the LOXL2 gene in HSC.Moreover,MSC-sEVmiR-4465 inhibited HSC activation and collagen expression by downregulating LOXL2 expression in vitro.MSC-sEVmiR-4465 injection could reduce HSC activation and collagen deposition in the CCl4-induced mouse model.MSC-sEVmiR-4465 mediating via LOXL2 also hindered the migration and invasion of HepG2 cells.In conclusion,we found that MSC-sEV can deliver miR-4465 into HSC to alleviate liver fibrosis via altering LOXL2,which might provide a promising therapeutic strategy for liver diseases.

关 键 词：Mesenchymal stem cell(MSC) Small extracellular vesicle(sEV) MicroRNA-4465(miR-4465) Hepatic stellate cell(HSC) Liver fibrosis 

分 类 号：R575.2[医药卫生—消化系统]