间充质干细胞衍生的外泌体通过调节NOD 1/NLRP3介导的上皮-间质转化和炎症来改善肺纤维化。

MSC-derived exosome ameliorates pulmonary fibrosis by modulating NOD 1/NLRP3-mediated epithelial-mesenchymal transition and inflammation.

作者信息

Chen Wei, Peng Jie, Tang Xiangyi, Ouyang Shao

机构信息

Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of University of South China, Hengyang, Hunan, China.

Department of Cardiovascular Medicine, The Second Affiliated Hospital of University of South China, Key Laboratory of Heart Failure Prevention & Treatment of Hengyang, Clinical Medicine Research Center of Arteriosclerotic Disease of Hunan Province, Hengyang, Hunan, China.

出版信息

Heliyon. 2024 Dec 26;11(2):e41436. doi: 10.1016/j.heliyon.2024.e41436. eCollection 2025 Jan 30.

DOI:10.1016/j.heliyon.2024.e41436

PMID:39872463

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11761938/

Abstract

BACKGROUND

Pulmonary fibrosis (PF) is an irreversible and usually fatal lung disease. In recent years, the therapeutic role of exosomes derived from mesenchymal stem cells (MSC-exos) in anti-fibrotic treatment has received much attention. In this study, we aimed to determine the anti-fibrotic properties and related molecular mechanisms of MSC-exos in Bleomycin(BLM)-induced PF.

METHODS

We used BLM-induced mice model of PF and in vitro model. MSC-exos were isolated from BMSCs cells using Exo Quick-TC kit and identified using conventional methods. Using cell counting kit-8 (CCK-8) to detect cell viability. Classic molecular biology approaches such as RT-qPCR, Western blot, immunofluorescence, and ELISA were used to examine molecular pathways. Histopathological examination was performed using HE and Masson staining.

RESULTS

MSC-exos alleviated inflammation, inhibited epithelial-mesenchymal transition (EMT), and ameliorated PF. Further studies showed that MSC-exos regulated NOD1/NF-kB signaling pathway to suppress the activation of NLRP3 inflammasomes both in vivo and in vitro. Additionally, overexpression of NLRP3 significantly reversed the anti-fibrotic effects of MSC-exos in BLM-induced lung epithelial cells.

CONCLUSION

MSC-derived exosome ameliorates pulmonary fibrosis by modulating NOD 1/NLRP3-mediated epithelial-mesenchymal transition and inflammation.

摘要

背景

肺纤维化（PF）是一种不可逆且通常致命的肺部疾病。近年来，间充质干细胞来源的外泌体（MSC-exos）在抗纤维化治疗中的作用备受关注。在本研究中，我们旨在确定MSC-exos在博来霉素（BLM）诱导的PF中的抗纤维化特性及相关分子机制。

方法

我们使用BLM诱导的PF小鼠模型和体外模型。使用Exo Quick-TC试剂盒从骨髓间充质干细胞（BMSCs）中分离MSC-exos，并采用常规方法进行鉴定。使用细胞计数试剂盒-8（CCK-8）检测细胞活力。采用RT-qPCR、蛋白质免疫印迹、免疫荧光和酶联免疫吸附测定等经典分子生物学方法检测分子通路。使用苏木精-伊红（HE）和Masson染色进行组织病理学检查。