MicroRNA-377-3p released by mesenchymal stem cell exosomes ameliorates lipopolysaccharide-induced acute lung injury by targeting RPTOR to induce autophagy

• Published in: Cell death & disease Vol. 11; no. 8; p. 657
• Main Authors: Wei, Xuxia, Yi, Xiaomeng, Lv, Haijin, Sui, Xin, Lu, Pinglan, Li, Lijuan, An, Yuling, Yang, Yang, Yi, Huimin, Chen, Guihua
• Format: Journal Article
• Language: English
• Published: England Springer Nature B.V 19.08.2020; Nature Publishing Group UK
• Subjects: Acute Lung Injury - genetics; Acute Lung Injury - physiopathology; Alveoli; Animals; Autophagy; Autophagy - genetics; Bronchus; Disease Models, Animal; Exosomes; Exosomes - genetics; Exosomes - metabolism; Fetuses; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Lung - metabolism; Lungs; Male; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal stem cells; Mesenchymal Stem Cells - metabolism; Mice; Mice, Inbred C57BL; MicroRNAs - genetics; MicroRNAs - physiology; miRNA; Morphometry; Phagocytosis; Regulatory-Associated Protein of mTOR - metabolism; Regulatory-Associated Protein of mTOR - physiology; Respiratory distress syndrome; Respiratory Distress Syndrome - metabolism; Respiratory failure; Stem cells; TOR protein; Umbilical cord
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-020-02857-4

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the severe lung damage and respiratory failure without effective therapy. However, there was a lack of understanding of the mechanism by which exosomes regulate autophagy during ALI/ARDS. Here, we found lipopolysaccharide (LPS) significantly increased inflammatory factors, administration of exosomes released by human umbilical cord mesenchymal stem cells (hucMSCs) successfully improved lung morphometry. Further studies showed that miR-377-3p in the exosomes played a pivotal role in regulating autophagy, leading to protect LPS induced ALI. Compared to exosomes released by human fetal lung fibroblast cells (HFL-1), hucMSCs-exosomes overexpressing miR-377-3p more effectively suppressed the bronchoalveolar lavage (BALF) and inflammatory factors and induced autophagy, causing recoveration of ALI. Administration of miR-377-3p expressing hucMSCs-exosomes or its target regulatory-associated protein of mTOR (RPTOR) knockdown significantly reduced ALI. In summary, miR-377-3p released by hucMSCs-exosomes ameliorated Lipopolysaccharide-induced acute lung injury by targeting RPTOR to induce autophagy in vivo and in vitro.