Wang LL, Ouyang MY, Yang ZE, Xing SN, Zhao S, Yu HY. Mesenchymal stem cells-derived exosomes alleviate radiation induced pulmonary fibrosis by inhibiting the protein kinase B/nuclear factor kappa B pathway. World J Stem Cells 2025; 17(6): 106488 [DOI: 10.4252/wjsc.v17.i6.106488]
Corresponding Author of This Article
Hui-Ying Yu, PhD, Laboratory of Basic Medicine, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang 110016, Liaoning Province, China. hyingy@sina.com
Research Domain of This Article
Medicine, Research & Experimental
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Stem Cells. Jun 26, 2025; 17(6): 106488 Published online Jun 26, 2025. doi: 10.4252/wjsc.v17.i6.106488
Mesenchymal stem cells-derived exosomes alleviate radiation induced pulmonary fibrosis by inhibiting the protein kinase B/nuclear factor kappa B pathway
Li-Li Wang, Ming-Yue Ouyang, Zi-En Yang, Si-Ning Xing, Song Zhao, Hui-Ying Yu, Laboratory of Basic Medicine, General Hospital of Northern Theater Command, Shenyang 110016, Liaoning Province, China
Author contributions: Wang LL and Yu HY designed the experiments; Wang LL, Ouyang MY, Yang ZE, Xing SN, and Zhao S performed the experiments; Wang LL, Ouyang MY, and Yang ZE analyzed the experiment data and wrote this manuscript; Yu HY reviewed the manuscript and supervised all the work. All authors have read and approved the final version of the manuscript.
Supported by Natural Science Foundation of Liaoning Province, No. 2024-MS-250.
Institutional review board statement: This study was approved by the Northern Theater Command General Hospital Ethics Committee [approval number: Y(2024)100].
Institutional animal care and use committee statement: All animal care and experimental procedures followed the National Research Council’s Guidelines for the Care and Use of Laboratory Animals and were approved by the Northern Theater Command General Hospital Ethics Committee (approval number: 2023-25).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: The data used to support the findings of this study are available from the corresponding author upon request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hui-Ying Yu, PhD, Laboratory of Basic Medicine, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang 110016, Liaoning Province, China. hyingy@sina.com
Received: February 28, 2025 Revised: April 14, 2025 Accepted: May 28, 2025 Published online: June 26, 2025 Processing time: 118 Days and 8 Hours
Abstract
BACKGROUND
Radiation induced pulmonary fibrosis (RIPF) is a long-term lung condition with a bleak outlook and few treatment possibilities. Mesenchymal stem cells (MSCs)-derived exosomes (MSCs-exosomes) possess tissue repair and regenerative properties, but their exact mechanisms in RIPF remain unclear. This study explores whether MSCs-exosomes can alleviate RIPF by modulating inflammation, extracellular matrix (ECM) accumulation, and epithelial-mesenchymal transition (EMT) via the protein kinase B (Akt)/nuclear factor kappa B (NF-κB) pathway.
AIM
To assess the therapeutic potential and mechanisms of MSCs-exosomes in RIPF.
METHODS
Sprague-Dawley rats were received 30 Gy X-ray radiation on the right chest to induce RIPF, while RLE-6TN and BEAS-2B cell lines were exposed to 10 Gy X-rays. Using differential centrifugation, MSCs-exosomes were isolated, and their protective effects were examined both in vivo and in vitro. Inflammatory cytokine concentrations were measured using Luminex liquid chip detection and enzyme linked immunosorbent assay. ECM and EMT-related proteins were analyzed using immunohistochemistry, western blotting, and real-time quantitative polymerase chain reaction. Western blotting and immunohistochemistry were also used to investigate the mechanisms underlying MSCs-exosomes’ effects in RIPF.
RESULTS
Administration of MSCs-exosomes significantly mitigated RIPF, reduced collagen deposition, and decreased levels of various inflammatory cytokines. Additionally, MSCs-exosomes prevented radiation-induced ECM accumulation and EMT. Treatment with MSCs-exosomes notably promoted cell proliferation, suppressed inflammation, and reversed ECM deposition and EMT in radiation-exposed alveolar epithelial cells. Mechanistic analysis further revealed that MSCs-exosomes exerted their anti-RIPF effects by inhibiting the Akt/NF-κB pathway, as shown in both in vivo and in vitro models.
CONCLUSION
MSCs-exosomes mitigate RIPF by suppressing inflammation, ECM deposition, and EMT through Akt/NF-κB inhibition, highlighting their potential as a therapeutic strategy.
Core Tip: Mesenchymal stem cells-derived exosomes were demonstrated protective properties against radiation induced pulmonary fibrosis in rat models and lung epithelial cell models. Moreover, these exosomes were shown to reverse the expression of key components involved in the buildup of extracellular matrix and epithelial-mesenchymal transition due to radiation by inhibiting the protein kinase B/nuclear factor kappa B pathway. This inhibition prevented fibrosis progression and facilitated the recovery and proliferation of damaged lung epithelial cells. These findings offer new insights into potential treatment strategies for radiation-induced pulmonary fibrosis.
