Extracellular vesicles derived from umbilical cord mesenchymal stromal cells alleviate pulmonary fibrosis by means of transforming growth factor-beta signaling inhibition

文献类型： 外文期刊

第一作者： Shi, Liyan

作者： Shi, Liyan;Li, Xiuying;Wang, Yimin;Shi, Liyan;Ren, Jing;Li, Jiping;Wang, Dongxu;Wang, Yusu;Zhang, Guokun;Li, Chunyi;Qin, Tao;Zhang, Guokun

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关键词： Extracellular vesicles; Umbilical cord-derived mesenchymal stromal cells; Pulmonary fibrosis; Transforming growth factor-β

期刊名称：STEM CELL RESEARCH & THERAPY （ 影响因子：5.116； 五年影响因子：5.554 ）

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年卷期： 2021 年 12 卷 1 期

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收录情况： SCI

摘要： Background Pulmonary fibrosis (PF), the end point of interstitial lung diseases, is characterized by myofibroblast over differentiation and excessive extracellular matrix accumulation, leading to progressive organ dysfunction and usually a terminal outcome. Studies have shown that umbilical cord-derived mesenchymal stromal cells (uMSCs) could alleviate PF; however, the underlying mechanism remains to be elucidated. Methods The therapeutic effects of uMSC-derived extracellular vesicles (uMSC-EVs) on PF were evaluated using bleomycin (BLM)-induced mouse models. Then, the role and mechanism of uMSC-EVs in inhibiting myofibroblast differentiation were investigated in vivo and in vitro. Results Treatment with uMSC-EVs alleviated the PF and enhanced the proliferation of alveolar epithelial cells in BLM-induced mice, thus improved the life quality, including the survival rate, body weight, fibrosis degree, and myofibroblast over differentiation of lung tissue. Moreover, these effects of uMSC-EVs on PF are likely achieved by inhibiting the transforming growth factor-beta (TGF-beta) signaling pathway, evidenced by decreased expression levels of TGF-beta 2 and TGF-beta R2. Using mimics of uMSC-EV-specific miRNAs, we found that miR-21 and miR-23, which are highly enriched in uMSC-EVs, played a critical role in inhibiting TGF-beta 2 and TGF-beta R2, respectively. Conclusion The effects of uMSCs on PF alleviation are likely achieved via EVs, which reveals a new role of uMSC-EV-derived miRNAs, opening a novel strategy for PF treatment in the clinical setting.

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