Xie Linshen, Zeng Ye
West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
Institute of Biomedical Engineering, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China.
Front Pharmacol. 2020 Dec 4;11:590972. doi: 10.3389/fphar.2020.590972. eCollection 2020.
Pulmonary fibrosis is closely associated with the recruitment of fibroblasts from capillary vessels with damaged endothelial cells, the epithelial mesenchymal transition (EMT) of type II alveolar epithelial cells, and the transformation of fibroblasts to myofibroblasts. Recent studies suggest that EMT is a key factor in the pathogenesis of pulmonary fibrosis, as the disruption of EMT-related effector molecules can inhibit the occurrence and development of PF. With the numerous advancements made in molecular biology in recent years, researchers have discovered that exosomes and their cargos, such as miRNAs, lncRNAs, and proteins, can promote or inhibit the EMT, modulate the transformation of fibroblasts into myofibroblasts, contribute to the proliferation of fibroblasts and promote immunoregulatory and mitochondrial damage during pulmonary fibrosis. Exosomes are key factors regulating the differentiation of bone marrow mesenchymal stem cells (BMSCs) into myofibroblasts. Interestingly, exosomes derived from BMSCs under pathological and physiological conditions may promote or inhibit the EMT of type II alveolar epithelial cells and the transformation of fibroblasts into myofibroblasts to regulate pulmonary fibrosis. Thus, exosomes may become a new direction in the study of drugs for the treatment of pulmonary fibrosis.
肺纤维化与来自内皮细胞受损的毛细血管的成纤维细胞募集、II型肺泡上皮细胞的上皮-间质转化（EMT）以及成纤维细胞向肌成纤维细胞的转变密切相关。最近的研究表明，EMT是肺纤维化发病机制中的关键因素，因为EMT相关效应分子的破坏可抑制PF的发生和发展。随着近年来分子生物学的众多进展，研究人员发现外泌体及其货物，如miRNA、lncRNA和蛋白质，可促进或抑制EMT，调节成纤维细胞向肌成纤维细胞的转化，促进成纤维细胞增殖，并在肺纤维化过程中促进免疫调节和线粒体损伤。外泌体是调节骨髓间充质干细胞（BMSC）向肌成纤维细胞分化的关键因素。有趣的是，病理和生理条件下源自BMSC的外泌体可能促进或抑制II型肺泡上皮细胞的EMT以及成纤维细胞向肌成纤维细胞的转化，从而调节肺纤维化。因此，外泌体可能成为治疗肺纤维化药物研究的新方向。
