Open AccessMesenchymal stem cell–secreted extracellular vesicles carrying TGF‐β1 up‐regulate miR‐132 and promote mouse M2 macrophage polarization
Author(s) -
Wang Yongqi,
Han Biao,
Wang Yingbin,
Wang Chunai,
Zhang Hong,
Xue Jianjun,
Wang Xiaoqing,
Niu Tingting,
Niu Zhen,
Chen Yuhe
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15860
Subject(s) - mesenchymal stem cell , microbiology and biotechnology , macrophage polarization , ubiquitin ligase , chemistry , extracellular vesicle , transforming growth factor , biology , tumor necrosis factor alpha , microrna , microvesicles , macrophage , ubiquitin , immunology , in vitro , biochemistry , gene
Abstract The effects of mesenchymal stem cells (MSCs) on different types of diseases are controversial, and the inner mechanisms remain unknown, which retards the utilization of MSCs in disease therapy. In this study, we aimed to elucidate the mechanisms of MSCs‐extracellular vesicles (EVs) carrying transforming growth factor‐beta 1 (TGF‐β1) in M2 polarization in mouse macrophages via the microRNA‐132 (miR‐132)/E3 ubiquitin ligase myc binding protein 2 (Mycbp2)/tuberous sclerosis complex 2 (TSC2) axis. Mouse MSCs were isolated for adipogenic and osteogenic induction, followed by co‐culture with mouse macrophages RAW264.7. Besides, mouse macrophages RAW264.7 were co‐cultured with MSCs‐EVs in vitro, where the proportion of macrophages and inflammation were detected by flow cytometry and ELISA. The experimental data revealed that MSCs‐EVs promoted M2 polarization of macrophages, and elevated interleukin (IL)‐10 expression and inhibited levels of IL‐1β, tumour necrosis factor (TNF)‐α and IL‐6. MSC‐EV‐treated macrophages RAW264.7 increased TGF‐β1 expression, thus elevating miR‐132 expression. MiR‐132 directly bound to Mycbp2, as confirmed by luciferase activity assay. Meanwhile, E3 ubiquitin ligase Mycbp2 could ubiquitinate TSC2 protein. Furthermore, silencing TGF‐β1 inhibited M2 polarization of MSC‐EV‐treated macrophages. Taken conjointly, this study provides evidence reporting that MSC‐secreted EVs carry TGF‐β1 to promote M2 polarization of macrophages via modulation of the miR‐132/Mycbp2/TSC2 axis.