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

MSC 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

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作者:Wei Chen, Jie Peng, Xiangyi Tang, Shao Ouyang

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.

Conclusion

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

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.

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