PMID- 35997581 OWN - NLM STAT- MEDLINE DCOM- 20221114 LR - 20231213 IS - 1522-7278 (Electronic) IS - 1520-4081 (Linking) VI - 37 IP - 12 DP - 2022 Dec TI - hUC-MSCs exosomal miR-451 alleviated acute lung injury by modulating macrophage M2 polarization via regulating MIF-PI3K-AKT signaling pathway. PG - 2819-2831 LID - 10.1002/tox.23639 [doi] AB - In the previous study, we have proved that exosomal miR-451 from human umbilical cord mesenchymal stem cells (hUC-MSCs) attenuated burn-induced acute lung injury (ALI). However, the mechanism of exosomal miR-451 in ALI remains unclear. Therefore, this study aimed to study the molecular mechanism of hUC-MSCs-derived exosomal miR-451 on ALI by regulating macrophage polarization. Exosomes were isolated and identified by transmission electron microscope (TEM) and nanoparticle tracking analysis (NTA). The expression of miR-451, macrophage migration inhibitory factor (MIF) and PI3K/AKT signaling pathway proteins were detected by qRT-PCR and western blot. Flow cytometry was used to detect the CD80 and CD206 positive cells. Severe burn rat model was established and HE was used to detect the inflammatory cell infiltration and inflammatory injury. Dual luciferase reporter system was used to detect the regulation of miR-451 to MIF. The contents of cytokines were detected by ELISA. The results showed that hUC-MSCs exosomes promoted macrophage M1 to M2 polarization. Furthermore, hUC-MSCs-derived exosomal miR-451 alleviated ALI development and promoted macrophage M1 to M2 polarization. Moreover, MIF was a direct target of miR-451. Downregulation of MIF regulated by miR-451 alleviated ALI development promoted macrophage M1 to M2 polarization. In addition, we found that MIF and hUC-MSCs-derived exosomal miR-451 participated in ALI by regulating PI3K/AKT signaling pathway. In conclusion, we indicated that hUC-MSCs-derived exosomal miR-451 alleviated ALI by modulating macrophage M2 polarization via regulating MIF-PI3K-AKT signaling pathway, which provided great scientific significance and clinical application value for the treatment of burn-induced ALI. CI - (c) 2022 Wiley Periodicals LLC. FAU - Liu, Jisong AU - Liu J AD - Department of Burn and Plastic Surgery, Third Hospital of Bengbu, Bengbu, Anhui, China. FAU - Xing, Fuxi AU - Xing F AD - Department of Burn and Plastic Surgery, Third Hospital of Bengbu, Bengbu, Anhui, China. FAU - Fu, Quanyou AU - Fu Q AD - Department of Burn and Plastic Surgery, Third Hospital of Bengbu, Bengbu, Anhui, China. FAU - He, Bo AU - He B AD - Department of Burn and Plastic Surgery, Third Hospital of Bengbu, Bengbu, Anhui, China. FAU - Jia, Zhigang AU - Jia Z AD - Department of Burn and Plastic Surgery, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China. FAU - Du, Juan AU - Du J AD - Department of Minimally Invasive Surgery, Third Hospital of Bengbu, Bengbu, Anhui, China. FAU - Li, Yong AU - Li Y AD - Department of Burn and Plastic Surgery, Third Hospital of Bengbu, Bengbu, Anhui, China. FAU - Zhang, Xiangzhou AU - Zhang X AD - Department of Burn and Plastic Surgery, Third Hospital of Bengbu, Bengbu, Anhui, China. FAU - Chen, Xulin AU - Chen X AUID- ORCID: 0000-0002-5182-2579 AD - Department of Burns, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China. LA - eng GR - ahwj2021a042/Key scientific research project of Anhui Provincial Health Commission in 2021/ GR - The tenth batch of "3221" industrial innovation and scientific research projects in Bengbu City/ PT - Journal Article DEP - 20220823 PL - United States TA - Environ Toxicol JT - Environmental toxicology JID - 100885357 RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - 0 (MicroRNAs) RN - EC 5.3.2.1 (MIF protein, human) RN - 0 (Macrophage Migration-Inhibitory Factors) RN - EC 5.3.- (Intramolecular Oxidoreductases) RN - 0 (MIRN451 microRNA, human) RN - EC 5.3.2.1 (Mif protein, rat) RN - 0 (MIRN451A microRNA, rat) SB - IM MH - Rats MH - Humans MH - Animals MH - Proto-Oncogene Proteins c-akt/metabolism MH - Phosphatidylinositol 3-Kinases/metabolism MH - *MicroRNAs/genetics/metabolism MH - *Mesenchymal Stem Cells/metabolism MH - *Acute Lung Injury/genetics/metabolism MH - Signal Transduction/genetics MH - Macrophages/metabolism MH - *Burns/genetics MH - *Macrophage Migration-Inhibitory Factors/genetics/metabolism MH - Intramolecular Oxidoreductases/genetics/metabolism OTO - NOTNLM OT - MIF OT - PI3K/AKT signaling pathway OT - acute lung injury OT - exosomal miR-451 OT - hUC-MSCs EDAT- 2022/08/24 06:00 MHDA- 2022/11/15 06:00 CRDT- 2022/08/23 09:43 PHST- 2022/08/01 00:00 [revised] PHST- 2022/03/23 00:00 [received] PHST- 2022/08/04 00:00 [accepted] PHST- 2022/08/24 06:00 [pubmed] PHST- 2022/11/15 06:00 [medline] PHST- 2022/08/23 09:43 [entrez] AID - 10.1002/tox.23639 [doi] PST - ppublish SO - Environ Toxicol. 2022 Dec;37(12):2819-2831. doi: 10.1002/tox.23639. Epub 2022 Aug 23.