Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 99, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2021.108075
Keywords
IPSC-derived exosomes; Pulmonary fibrosis; miR-302a-3p; TET1; M2-type macrophages
Categories
Funding
- Youth Fund Project of National Natural Science Foundation of China [81400042]
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In a mouse model of pulmonary fibrosis, iPSC-exosomes were found to alleviate fibrosis by delivering miR-302a-3p to inhibit M2-type macrophages.
Idiopathic pulmonary fibrosis (PF) is a type of chronic lung disease. Here, we investigated the effect of induced pluripotent stem cell (iPSC)-derived exosomes (iPSC-exosomes) on M2-type macrophages which play a critical role in pulmonary fibrosis. Exosomes were purified from the conditioned medium of iPSCs. Mice models of pulmonary fibrosis were established by intratracheal instillation with 5 mg/kg bleomycin. Thereafter, the histopathological changes and collagen deposition were detected by HE and masson staining. Meanwhile the level of M2-type macrophages was elevated by immunofluorescence staining with F4/80 and Arg-1. Luciferase reporter assay was conducted to verify the binding of miR-302a-3p to ten-eleven translocation 1 (TET1). Our results showed that, after treatment with iPSC-exosomes, the pulmonary fibrosis induced by bleomycin was relieved, with less collagen deposition. In addition, the increased M2-type macrophages in PF mice were reduced upon treatment with iPSC-exosomes. Moreover, we found that the iPSC-exosomes showed higher level of miR302a-3p. Interestingly, the level of miR-302a-3p in the lungs of PF mice was increased upon treatment with iPSC-exosomes. Furthermore, we verified that TET1 was a direct target of miR-302a-3p. Up-regulation of miR302a-3p or TET1 silencing repressed M2-type macrophages. Down-regulation of miR-302a-3p abolished the beneficial effects of iPSC-exosomes on pulmonary fibrosis. Collectively, our study revealed that iPSC-exosomes delivered miR-302a-3p to suppress the M2-type macrophages via targeting TET1, thus mitigating pulmonary fibrosis. This study indicates that iPSC-exosomes may become a potential therapeutic agent for pulmonary fibrosis.
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