PMID- 33413595
OWN - NLM
STAT- MEDLINE
DCOM- 20210705
LR  - 20220531
IS  - 1757-6512 (Electronic)
IS  - 1757-6512 (Linking)
VI  - 12
IP  - 1
DP  - 2021 Jan 7
TI  - microRNA-27b shuttled by mesenchymal stem cell-derived exosomes prevents sepsis 
      by targeting JMJD3 and downregulating NF-kappaB signaling pathway.
PG  - 14
LID - 10.1186/s13287-020-02068-w [doi]
LID - 14
AB  - BACKGROUND: Exosomal microRNAs (miRs) derived from mesenchymal stem cells (MSCs) 
      have been shown to play roles in the pathophysiological processes of sepsis. 
      Moreover, miR-27b is highly enriched in MSC-derived exosomes. Herein, we aimed to 
      investigate the potential role and downstream molecular mechanism of exosomal 
      miR-27b in sepsis. METHODS: Inflammation was induced in bone marrow-derived 
      macrophages (BMDMs) by lipopolysaccharide (LPS), and mice were made septic by 
      cecal ligation and puncture (CLP). The expression pattern of miR-27b in 
      MSC-derived exosomes was characterized using RT-qPCR, and its downstream gene was 
      predicted by in silico analysis. The binding affinity between miR-27b, Jumonji D3 
      (JMJD3), or nuclear factor kappaB (NF-kappaB) was characterized to identify the 
      underlying mechanism. We induced miR-27b overexpression or downregulation, along 
      with silencing of JMJD3 or NF-kappaB to examine their effects on sepsis. The 
      production of pro-inflammatory cytokines TNF-alpha, IL-1beta, and IL-6 was detected by 
      ELISA. RESULTS: miR-27b was highly expressed in MSC-derived exosomes. Mechanistic 
      investigations showed that miR-27b targeted JMJD3. miR-27b decreased expression 
      of pro-inflammatory genes by inhibiting the recruitment of JMJD3 and NF-kappaB at 
      gene promoter region. Through this, MSC-derived exosomal miR-27b diminished 
      production of pro-inflammatory cytokines in LPS-treated BMDMs and septic mice, 
      which could be rescued by upregulation of JMJD3 and NF-kappaB. Besides, in vitro 
      findings were reproduced by in vivo findings. CONCLUSION: These data demonstrated 
      that exosomal miR-27b derived from MSCs inhibited the development of sepsis by 
      downregulating JMJD3 and inactivating the NF-kappaB signaling pathway.
FAU - Sun, Jia
AU  - Sun J
AD  - ShenZhen Beike Biotechnology Research Institute, No. 59, Gaoxin South 9th Road, 
      Nanshan District, Shenzhen, 518057, Guangdong Province, People's Republic of 
      China.
AD  - Intervention and Cell Therapy Center, Shenzhen Hospital of Peking University, 
      Shenzhen, 518057, People's Republic of China.
FAU - Sun, Xuan
AU  - Sun X
AD  - Hematology Department, Shenzhen People's Hospital, Shenzhen, 518020, People's 
      Republic of China.
FAU - Chen, Junhui
AU  - Chen J
AD  - Intervention and Cell Therapy Center, Shenzhen Hospital of Peking University, 
      Shenzhen, 518057, People's Republic of China.
FAU - Liao, Xin
AU  - Liao X
AD  - ShenZhen Beike Biotechnology Research Institute, No. 59, Gaoxin South 9th Road, 
      Nanshan District, Shenzhen, 518057, Guangdong Province, People's Republic of 
      China.
FAU - He, Yixuan
AU  - He Y
AD  - ShenZhen Beike Biotechnology Research Institute, No. 59, Gaoxin South 9th Road, 
      Nanshan District, Shenzhen, 518057, Guangdong Province, People's Republic of 
      China.
FAU - Wang, Jinsong
AU  - Wang J
AD  - ShenZhen Beike Biotechnology Research Institute, No. 59, Gaoxin South 9th Road, 
      Nanshan District, Shenzhen, 518057, Guangdong Province, People's Republic of 
      China.
FAU - Chen, Rui
AU  - Chen R
AD  - ShenZhen Beike Biotechnology Research Institute, No. 59, Gaoxin South 9th Road, 
      Nanshan District, Shenzhen, 518057, Guangdong Province, People's Republic of 
      China.
FAU - Hu, Sean
AU  - Hu S
AD  - ShenZhen Beike Biotechnology Research Institute, No. 59, Gaoxin South 9th Road, 
      Nanshan District, Shenzhen, 518057, Guangdong Province, People's Republic of 
      China. junyuanhu0507res@163.com.
AD  - Clinical Medical Research Center, Shenzhen People's Hospital, Shenzhen, 518020, 
      People's Republic of China. junyuanhu0507res@163.com.
FAU - Qiu, Chen
AU  - Qiu C
AD  - Respiratory and Critical Care Medicine Department, Shenzhen People's Hospital, 
      No. 1017, Dongmen North Road, Luohu District, Shenzhen, 518020, Guangdong 
      Province, People's Republic of China. szchester@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210107
PL  - England
TA  - Stem Cell Res Ther
JT  - Stem cell research & therapy
JID - 101527581
RN  - 0 (MicroRNAs)
RN  - 0 (NF-kappa B)
RN  - EC 1.14.11.- (Jumonji Domain-Containing Histone Demethylases)
RN  - EC 1.5.- (Kdm6b protein, mouse)
SB  - IM
MH  - Animals
MH  - *Exosomes/genetics/metabolism
MH  - Jumonji Domain-Containing Histone Demethylases
MH  - *Mesenchymal Stem Cells/metabolism
MH  - Mice
MH  - *MicroRNAs/genetics
MH  - NF-kappa B/genetics/metabolism
MH  - *Sepsis/genetics
MH  - Signal Transduction
PMC - PMC7791667
OTO - NOTNLM
OT  - Exosome
OT  - Jumonji D3
OT  - Mesenchymal stem cells
OT  - MicroRNA-27b
OT  - Nuclear factor kappaB/p65
OT  - Sepsis
COIS- The authors declare that they have no competing interests.
EDAT- 2021/01/09 06:00
MHDA- 2021/07/06 06:00
PMCR- 2021/01/07
CRDT- 2021/01/08 05:47
PHST- 2020/04/26 00:00 [received]
PHST- 2020/12/02 00:00 [accepted]
PHST- 2021/01/08 05:47 [entrez]
PHST- 2021/01/09 06:00 [pubmed]
PHST- 2021/07/06 06:00 [medline]
PHST- 2021/01/07 00:00 [pmc-release]
AID - 10.1186/s13287-020-02068-w [pii]
AID - 2068 [pii]
AID - 10.1186/s13287-020-02068-w [doi]
PST - epublish
SO  - Stem Cell Res Ther. 2021 Jan 7;12(1):14. doi: 10.1186/s13287-020-02068-w.