PMID- 32814765 OWN - NLM STAT- MEDLINE DCOM- 20210413 LR - 20220418 IS - 2041-4889 (Electronic) VI - 11 IP - 8 DP - 2020 Aug 19 TI - MicroRNA-377-3p released by mesenchymal stem cell exosomes ameliorates lipopolysaccharide-induced acute lung injury by targeting RPTOR to induce autophagy. PG - 657 LID - 10.1038/s41419-020-02857-4 [doi] LID - 657 AB - 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. FAU - Wei, Xuxia AU - Wei X AD - Surgical and Transplant Intensive Care Unit, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600, Tianhe Road, Tianhe District, Guangzhou, 510630, Guangdong, People's Republic of China. FAU - Yi, Xiaomeng AU - Yi X AD - Surgical and Transplant Intensive Care Unit, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600, Tianhe Road, Tianhe District, Guangzhou, 510630, Guangdong, People's Republic of China. FAU - Lv, Haijin AU - Lv H AUID- ORCID: 0000-0001-5590-8874 AD - Surgical and Transplant Intensive Care Unit, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600, Tianhe Road, Tianhe District, Guangzhou, 510630, Guangdong, People's Republic of China. FAU - Sui, Xin AU - Sui X AD - Surgical and Transplant Intensive Care Unit, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600, Tianhe Road, Tianhe District, Guangzhou, 510630, Guangdong, People's Republic of China. FAU - Lu, Pinglan AU - Lu P AD - Surgical and Transplant Intensive Care Unit, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600, Tianhe Road, Tianhe District, Guangzhou, 510630, Guangdong, People's Republic of China. FAU - Li, Lijuan AU - Li L AD - Surgical and Transplant Intensive Care Unit, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600, Tianhe Road, Tianhe District, Guangzhou, 510630, Guangdong, People's Republic of China. FAU - An, Yuling AU - An Y AD - Surgical and Transplant Intensive Care Unit, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600, Tianhe Road, Tianhe District, Guangzhou, 510630, Guangdong, People's Republic of China. FAU - Yang, Yang AU - Yang Y AD - Department of Hepatic Surgery and Liver transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University; Organ Transplantation Research Center of Guangdong Province, Guangdong province engineering laboratory for transplantation medicine, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600, Tianhe Road, Tianhe District, Guangzhou, 510630, Guangdong, People's Republic of China. yangy5@mail.sysu.edu.cn. FAU - Yi, Huimin AU - Yi H AD - Surgical and Transplant Intensive Care Unit, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600, Tianhe Road, Tianhe District, Guangzhou, 510630, Guangdong, People's Republic of China. ylhmin@hotmail.com. FAU - Chen, Guihua AU - Chen G AD - Department of Hepatic Surgery and Liver transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University; Organ Transplantation Research Center of Guangdong Province, Guangdong province engineering laboratory for transplantation medicine, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600, Tianhe Road, Tianhe District, Guangzhou, 510630, Guangdong, People's Republic of China. chghua@mail.sysu.edu.cn. LA - eng PT - Journal Article DEP - 20200819 PL - England TA - Cell Death Dis JT - Cell death & disease JID - 101524092 RN - 0 (Lipopolysaccharides) RN - 0 (MIRN377 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RPTOR protein, human) RN - 0 (Regulatory-Associated Protein of mTOR) SB - IM EIN - Cell Death Dis. 2020 Sep 12;11(9):746. PMID: 32920597 MH - Acute Lung Injury/*genetics/physiopathology MH - Animals MH - Autophagy/genetics MH - Disease Models, Animal MH - Exosomes/genetics/metabolism MH - Human Umbilical Vein Endothelial Cells MH - Humans MH - Lipopolysaccharides/pharmacology MH - Lung/metabolism MH - Male MH - Mesenchymal Stem Cell Transplantation/methods MH - Mesenchymal Stem Cells/metabolism MH - Mice MH - Mice, Inbred C57BL MH - MicroRNAs/*genetics/physiology MH - Regulatory-Associated Protein of mTOR/*metabolism/physiology MH - Respiratory Distress Syndrome/metabolism PMC - PMC7438519 COIS- The authors declare that they have no conflict of interest. EDAT- 2020/08/21 06:00 MHDA- 2021/04/14 06:00 PMCR- 2020/08/19 CRDT- 2020/08/21 06:00 PHST- 2020/03/04 00:00 [received] PHST- 2020/07/31 00:00 [accepted] PHST- 2020/07/31 00:00 [revised] PHST- 2020/08/21 06:00 [entrez] PHST- 2020/08/21 06:00 [pubmed] PHST- 2021/04/14 06:00 [medline] PHST- 2020/08/19 00:00 [pmc-release] AID - 10.1038/s41419-020-02857-4 [pii] AID - 2857 [pii] AID - 10.1038/s41419-020-02857-4 [doi] PST - epublish SO - Cell Death Dis. 2020 Aug 19;11(8):657. doi: 10.1038/s41419-020-02857-4.