PMID- 32965772
OWN - NLM
STAT- MEDLINE
DCOM- 20210504
LR  - 20210504
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 24
IP  - 21
DP  - 2020 Nov
TI  - Mesenchymal stem cell-secreted extracellular vesicles carrying TGF-beta1 up-regulate 
      miR-132 and promote mouse M2 macrophage polarization.
PG  - 12750-12764
LID - 10.1111/jcmm.15860 [doi]
AB  - 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-beta1) 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-1beta, tumour necrosis factor (TNF)-alpha 
      and IL-6. MSC-EV-treated macrophages RAW264.7 increased TGF-beta1 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-beta1 inhibited M2 
      polarization of MSC-EV-treated macrophages. Taken conjointly, this study provides 
      evidence reporting that MSC-secreted EVs carry TGF-beta1 to promote M2 polarization 
      of macrophages via modulation of the miR-132/Mycbp2/TSC2 axis.
CI  - (c) 2020 The Authors. Journal of Cellular and Molecular Medicine published by 
      Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
FAU - Wang, Yongqi
AU  - Wang Y
AUID- ORCID: 0000-0001-7889-2262
AD  - Department of Anesthesiology, the First Hospital of Lanzhou University, Lanzhou, 
      China.
FAU - Han, Biao
AU  - Han B
AD  - Department of Thoracic Surgery, the First Hospital of Lanzhou University, 
      Lanzhou, China.
FAU - Wang, Yingbin
AU  - Wang Y
AD  - Department of Anesthesiology, Lanzhou University Second Hospital, Lanzhou, China.
FAU - Wang, Chunai
AU  - Wang C
AD  - Department of Anesthesiology, Gansu Provincial Hospital of TCM, Lanzhou, China.
FAU - Zhang, Hong
AU  - Zhang H
AD  - Department of Anesthesiology, the First Hospital of Lanzhou University, Lanzhou, 
      China.
FAU - Xue, Jianjun
AU  - Xue J
AD  - Department of Anesthesiology, Gansu Provincial Hospital of TCM, Lanzhou, China.
FAU - Wang, Xiaoqing
AU  - Wang X
AD  - Department of Anesthesiology, the First Hospital of Lanzhou University, Lanzhou, 
      China.
FAU - Niu, Tingting
AU  - Niu T
AD  - The First School of Clinical Medicine, the First Hospital of Lanzhou University, 
      Lanzhou, China.
FAU - Niu, Zhen
AU  - Niu Z
AD  - The First School of Clinical Medicine, the First Hospital of Lanzhou University, 
      Lanzhou, China.
FAU - Chen, Yuhe
AU  - Chen Y
AD  - The First School of Clinical Medicine, the First Hospital of Lanzhou University, 
      Lanzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200923
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (Lipopolysaccharides)
RN  - 0 (MIRN132 microRNA, mouse)
RN  - 0 (MicroRNAs)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (Tsc2 protein, mouse)
RN  - 0 (Tuberous Sclerosis Complex 2 Protein)
RN  - EC 2.3.2.27 (Mycbp2 protein, mouse)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cell Polarity/*genetics
MH  - Cell Separation
MH  - Down-Regulation/genetics
MH  - Extracellular Vesicles/*metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Lipopolysaccharides
MH  - Macrophages/*cytology/*metabolism
MH  - Mesenchymal Stem Cells/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/*genetics/metabolism
MH  - Models, Biological
MH  - Phenotype
MH  - Proteolysis
MH  - RAW 264.7 Cells
MH  - Transforming Growth Factor beta1/*metabolism
MH  - Tuberous Sclerosis Complex 2 Protein/metabolism
MH  - Ubiquitin-Protein Ligases/metabolism
MH  - Ubiquitination
MH  - Up-Regulation/*genetics
PMC - PMC7686990
OTO - NOTNLM
OT  - M2 polarization
OT  - Mycbp2
OT  - TGF-beta1
OT  - TSC2
OT  - extracellular vesicles
OT  - macrophages
OT  - mesenchymal stem cells
OT  - microRNA-132
COIS- The authors declare that there is no conflict of interest associated with the 
      manuscript.
EDAT- 2020/09/24 06:00
MHDA- 2021/05/05 06:00
PMCR- 2020/11/01
CRDT- 2020/09/23 12:16
PHST- 2020/04/07 00:00 [received]
PHST- 2020/08/19 00:00 [revised]
PHST- 2020/08/21 00:00 [accepted]
PHST- 2020/09/24 06:00 [pubmed]
PHST- 2021/05/05 06:00 [medline]
PHST- 2020/09/23 12:16 [entrez]
PHST- 2020/11/01 00:00 [pmc-release]
AID - JCMM15860 [pii]
AID - 10.1111/jcmm.15860 [doi]
PST - ppublish
SO  - J Cell Mol Med. 2020 Nov;24(21):12750-12764. doi: 10.1111/jcmm.15860. Epub 2020 
      Sep 23.