Microvesicles derived from mesenchymal stem cells inhibit acute respiratory distress syndrome-related pulmonary fibrosis in mouse partly through hepatocyte growth factor  

作　　者：Qi-Hong Chen Ying Zhang Xue Gu Peng-Lei Yang Jun Yuan Li-Na Yu Jian-Mei Chen 

机构地区：[1]Department of Critical Care Medicine,Jiangdu People’s Hospital of Yangzhou,Jiangdu People’s Hospital Affiliated to Yangzhou University,Yangzhou 225200,Jiangsu Province,China [2]Department of Critical Care Medicine,Jiangdu People’s Hospital of Yangzhou,Yangzhou 225200,Jiangsu Province,China [3]Institute of Translational Medicine,Medical College,Yangzhou University,Yangzhou 225000,Jiangsu Province,China

出　　处：《World Journal of Stem Cells》2024年第8期811-823,共13页世界干细胞杂志（英文版）（电子版）

基　　金：Research Project of Jiangsu Provincial Health Commission,No.Z2022008;and Research Project of Yangzhou Health Commission,No.2023-2-27.

摘　　要：BACKGROUND Pulmonary fibrosis is one of the main reasons for the high mortality rate among acute respiratory distress syndrome(ARDS)patients.Mesenchymal stromal cell-derived microvesicles(MSC-MVs)have been shown to exert antifibrotic effects in lung diseases.AIM To investigate the effects and mechanisms of MSC-MVs on pulmonary fibrosis in ARDS mouse models.METHODS MSC-MVs with low hepatocyte growth factor(HGF)expression(siHGF-MSC-MVs)were obtained via lentivirus transfection and used to establish the ARDS pulmonary fibrosis mouse model.Following intubation,respiratory mechanics-related indicators were measured via an experimental small animal lung function tester.Homing of MSC-MVs in lung tissues was investigated by near-infrared live imaging.Immunohistochemical,western blotting,ELISA and other methods were used to detect expression of pulmonary fibrosis-related proteins and to compare effects on pulmonary fibrosis and fibrosis-related indicators.RESULTS The MSC-MVs gradually migrated and homed to damaged lung tissues in the ARDS model mice.Treatment with MSC-MVs significantly reduced lung injury and pulmonary fibrosis scores.However,low expression of HGF(siHGF-MSC-MVs)significantly inhibited the effects of MSC-MVs(P<0.05).Compared with the ARDS pulmonary fibrosis group,the MSC-MVs group exhibited suppressed expression of type I collagen antigen,type III collagen antigen,and the proteins transforming growth factor-βandα-smooth muscle actin,whereas the siHGF-MVs group exhibited significantly increased expression of these proteins.In addition,pulmonary compliance and the pressure of oxygen/oxygen inhalation ratio were significantly lower in the MSC-MVs group,and the effects of the MSC-MVs were significantly inhibited by low HGF expression(all P<0.05).CONCLUSION MSC-MVs improved lung ventilation functions and inhibited pulmonary fibrosis in ARDS mice partly via HGF mRNA transfer.

关 键 词：Microvesicles derived from mesenchymal stem cells Acute respiratory distress syndrome Pulmonary fibrosis Hepatocyte growth factor Mesenchymal stromal cells 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]