Mouse mesenchymal stem cell-derived exosomal miR-205-5p modulates LPS-induced macrophage polarization and alleviates lung injury by regulating the USP7/FOXM1 axis.

IF 5.7 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Yinglu Feng, Min Tang, Haopeng Li, Shanglong Yao, Bo Li
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引用次数: 0

Abstract

Exosomal microRNAs produced from mesenchymal stem cells (MSCs) are crucial in the management of acute lung injury (ALI). In this work, mMSCs separated from bone marrow were used to extract exosomes (MSC-Exos). MSC-Exos treatment attenuated pathological changes and scores, and edema in ALI mice. Also, MSC-Exos administration modulated the concentrations of inflammatory factors as well as the macrophage polarization both in vivo and in vitro. Upregulation of miR-205-5p in MSC-Exos regulated the macrophage polarization and the contents of inflammatory factors in animal and cell models. MiR-205-5p targeted USP7, and negatively modulated the expression of USP7. USP7 interacted with FOXM1, and reduced the ubiquitination degradation of FOXM1. MSC-derived exosomal miR-205-5p modulated ubiquitination of FOXM1 by targeting USP7. The ameliorative effect of MSC-Exos on the macrophage polarization and the inflammatory factors release was reversed with the overexpression of USP7 in animal and cell models. Collectively, MSC-derived exosomal miR-205-5p regulated lipopolysaccharide (LPS)-induced macrophage polarization and alleviated lung injury by the USP7/FOXM1 axis, which developed a potential target for the treatment of ALI.

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来源期刊
Drug Delivery and Translational Research
Drug Delivery and Translational Research MEDICINE, RESEARCH & EXPERIMENTALPHARMACOL-PHARMACOLOGY & PHARMACY
CiteScore
11.70
自引率
1.90%
发文量
160
期刊介绍: The journal provides a unique forum for scientific publication of high-quality research that is exclusively focused on translational aspects of drug delivery. Rationally developed, effective delivery systems can potentially affect clinical outcome in different disease conditions. Research focused on the following areas of translational drug delivery research will be considered for publication in the journal. Designing and developing novel drug delivery systems, with a focus on their application to disease conditions; Preclinical and clinical data related to drug delivery systems; Drug distribution, pharmacokinetics, clearance, with drug delivery systems as compared to traditional dosing to demonstrate beneficial outcomes Short-term and long-term biocompatibility of drug delivery systems, host response; Biomaterials with growth factors for stem-cell differentiation in regenerative medicine and tissue engineering; Image-guided drug therapy, Nanomedicine; Devices for drug delivery and drug/device combination products. In addition to original full-length papers, communications, and reviews, the journal includes editorials, reports of future meetings, research highlights, and announcements pertaining to the activities of the Controlled Release Society.
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