PMID- 32821084
OWN - NLM
STAT- MEDLINE
DCOM- 20210701
LR  - 20220416
IS  - 1177-8881 (Electronic)
IS  - 1177-8881 (Linking)
VI  - 14
DP  - 2020
TI  - Exosomes Derived from MicroRNA-146a-5p-Enriched Bone Marrow Mesenchymal Stem 
      Cells Alleviate Intracerebral Hemorrhage by Inhibiting Neuronal Apoptosis and 
      Microglial M1 Polarization.
PG  - 3143-3158
LID - 10.2147/DDDT.S255828 [doi]
AB  - INTRODUCTION: Intracerebral hemorrhage (ICH) is a devastating type of stroke with 
      high mortality, and the effective therapies for ICH remain to be explored. 
      Exosomes (Exos) have been found to play important roles in cell communication by 
      transferring molecules, including microRNAs (miRNAs/miRs). MiRNAs are critical 
      regulators of genes involved in many various biological processes and have been 
      demonstrated to aggravate or alleviate brain damages induced by ICH. The aim of 
      the present study was to investigate the effect of Exos derived from 
      miR-146a-5p-enriched bone marrow mesenchymal stem cells (BMSCs-miR-146a-5p-Exos) 
      on experimental ICH. METHODS: ICH was induced in adult male Sprague-Dawley rats 
      by an intrastriatal injection of collagenase type IV. At 24 h after surgery, Exos 
      were administrated. For detecting apoptotic cells, TUNEL staining was performed 
      using an in situ Cell Death Detection Kit. Fluoro-Jade B staining was performed 
      to detect degenerating neurons. Immunofluorescence assay was performed to detect 
      the expression of myeloperoxidase (MPO) and OX-42. The binding of miR-146a-5p and 
      its target genes was confirmed by luciferase reporter assay. RESULTS: At 24 h 
      after surgery, BMSCs-miR-146a-5p-Exos administration significantly improved 
      neurological function, reduced apoptotic and degenerative neurons, and inhibited 
      inflammatory response. Furthermore, miR-146a-5p-enriched Exos obviously inhibited 
      the M1 polarization of microglia after ICH in rats, accompanied by the reduced 
      expression of pro-inflammatory mediators releasing by M1 microglia including 
      inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and monocyte 
      chemoattractant protein-1 (MCP-1). Finally, we observed that miR-146a-5p directly 
      targeted interleukin-1 receptor-associated kinase1 (IRAK1) and nuclear factor of 
      activated T cells 5 (NFAT5), which contributed to the inflammation response and 
      the polarization of M1 microglia/macrophages. CONCLUSION: We demonstrated that 
      miR-146a-5p-riched BMSCs-Exos could offer neuroprotection and functional 
      improvements after ICH through reducing neuronal apoptosis, and inflammation 
      associated with the inhibition of microglial M1 polarization by downregulating 
      the expression of IRAK1 and NFAT5.
CI  - (c) 2020 Duan et al.
FAU - Duan, Shurong
AU  - Duan S
AD  - Department of Neurology, The First Affiliated Hospital of Harbin Medical 
      University, Harbin 150001, People's Republic of China.
FAU - Wang, Fei
AU  - Wang F
AD  - Department of Neurology, The First Affiliated Hospital of Harbin Medical 
      University, Harbin 150001, People's Republic of China.
FAU - Cao, Jingwei
AU  - Cao J
AD  - Department of Neurology, The First Affiliated Hospital of Harbin Medical 
      University, Harbin 150001, People's Republic of China.
FAU - Wang, Chunyan
AU  - Wang C
AD  - Department of Neurology, The First Affiliated Hospital of Harbin Medical 
      University, Harbin 150001, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20200805
PL  - New Zealand
TA  - Drug Des Devel Ther
JT  - Drug design, development and therapy
JID - 101475745
RN  - 0 (MIRN146 microRNA, rat)
RN  - 0 (MicroRNAs)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Cerebral Hemorrhage/chemically induced/*metabolism
MH  - Exosomes/*metabolism
MH  - Injections, Intraventricular
MH  - Male
MH  - Matrix Metalloproteinase 9/administration & dosage/metabolism
MH  - Mesenchymal Stem Cells/*metabolism
MH  - MicroRNAs/*metabolism
MH  - Microglia/*metabolism
MH  - Neurons/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
PMC - PMC7425091
OTO - NOTNLM
OT  - apoptosis
OT  - exosomes
OT  - intracerebral hemorrhage
OT  - microRNA-146a-5p
OT  - microglial M1 polarization
COIS- The authors have no conflicts of interest to declare.
EDAT- 2020/08/22 06:00
MHDA- 2021/07/02 06:00
PMCR- 2020/08/05
CRDT- 2020/08/22 06:00
PHST- 2020/03/27 00:00 [received]
PHST- 2020/07/03 00:00 [accepted]
PHST- 2020/08/22 06:00 [entrez]
PHST- 2020/08/22 06:00 [pubmed]
PHST- 2021/07/02 06:00 [medline]
PHST- 2020/08/05 00:00 [pmc-release]
AID - 255828 [pii]
AID - 10.2147/DDDT.S255828 [doi]
PST - epublish
SO  - Drug Des Devel Ther. 2020 Aug 5;14:3143-3158. doi: 10.2147/DDDT.S255828. 
      eCollection 2020.