MicroRNA-451 from Human Umbilical Cord-Derived Mesenchymal Stem Cell Exosomes Inhibits Alveolar Macrophage Autophagy via Tuberous Sclerosis Complex 1/Mammalian Target of Rapamycin Pathway to Attenuate Burn-Induced Acute Lung Injury in Rats

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外文摘要：Objective Our previous studies established that microRNA (miR)-451 from human umbilical cord mesenchymal stem cell-derived exosomes (hUC-MSC-Exos) alleviates acute lung injury (ALI). This study aims to elucidate the mechanisms by which miR-451 in hUC-MSC-Exos reduces ALI by modulating macrophage autophagy.Methods Exosomes were isolated from hUC-MSCs. Severe burn-induced ALI rat models were treated with hUC-MSC-Exos carrying the miR-451 inhibitor. Hematoxylin-eosin staining evaluated inflammatory injury. Enzyme-linked immunosorbnent assay measured lipopolysaccharide (LPS),tumor necrosis factor-α,and interleukin-1β levels. qRT-PCR detected miR-451 and tuberous sclerosis complex 1 (TSC1) expressions. The regulatory role of miR-451 on TSC1 was determined using a dual-luciferase reporter system. Western blotting determined TSC1 and proteins related to the mammalian target of rapamycin (mTOR) pathway and autophagy. Immunofluorescence analysis was conducted to examine exosomes phagocytosis in alveolar macrophages and autophagy level.Results hUC-MSC-Exos with miR-451 inhibitor reduced burn-induced ALI and promoted macrophage autophagy. MiR-451 could be transferred from hUC-MSCs to alveolar macrophages via exosomes and directly targeted TSC1. Inhibiting miR-451 in hUC-MSC-Exos elevated TSC1 expression and inactivated the mTOR pathway in alveolar macrophages. Silencing TSC1 activated mTOR signaling and inhibited autophagy,while TSC1 knockdown reversed the autophagy from the miR-451 inhibitor-induced.Conclusion miR-451 from hUC-MSC exosomes improves ALI by suppressing alveolar macrophage autophagy through modulation of the TSC1/mTOR pathway,providing a potential therapeutic strategy for ALI.

外文关键词：

Acute lung injuryHuman umbilical cord mesenchymal stem cell-derived exosomesMicroRNA-451Tuberous sclerosis complex 1Mammalian target of rapamycin pathwayAutophagy

作者：

Zhigang Jia、Lin Li、Peng Zhao、Guo Fei、Shuangru Li、Qinqin Song、Guangpeng Liu、Jisong Liu

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作者单位：

Affiliated Hospital of Jiang nan University,Department of Burn and Plastic Surgery,Wuxi 214000,Jiangsu,China

The Third People's Hospital of Bengbu Affiliated to Bengbu Medical University,Department of Burn and Plastic Surgery,Bengbu 230000,Anhui,China

基金：

tenth batch of"3221"industrial innovation and scientific research projects in Bengbu City2021 Bengbu Medical College Science and Technology Project

项目编号：

beng talent[2020]8021byzd217

出版年：

2024

DOI：

10.3967/bes2024.128

生物医学与环境科学(英文版)

中国疾病预防控制中心

生物医学与环境科学(英文版)

CSTPCD

影响因子：0.76

ISSN：0895-3988

年,卷(期)：2024.37(9)