PMID- 22714950
OWN - NLM
STAT- MEDLINE
DCOM- 20130228
LR  - 20220330
IS  - 1549-4918 (Electronic)
IS  - 1066-5099 (Linking)
VI  - 30
IP  - 8
DP  - 2012 Aug
TI  - MicroRNA-181a regulates local immune balance by inhibiting proliferation and 
      immunosuppressive properties of mesenchymal stem cells.
PG  - 1756-70
LID - 10.1002/stem.1156 [doi]
AB  - Mesenchymal stem cells (MSCs) exhibit extensive self-renewal potential and can 
      modulate immunocyte activation. Our previous study reported that miR-181a 
      expression was significantly increased in placenta from women with severe 
      preeclampsia (PE), but the mechanisms by which miR-181a regulates MSCs are 
      unknown. In this study, we asked if and how miR-181a regulates MSCs' 
      proliferation and immunosuppressive properties. We found that the expression of 
      miR-181a in the MSCs derived from the umbilical cord and decidua of PE patients 
      increased relative to MSCs derived from normal patients. Transfection with 
      miR-181a oligos prevented MSCs proliferation but did not affect MSCs apoptosis. 
      Overexpression of miR-181a blocked activation of the TGF-beta signaling pathway and 
      caused downregulation of target gene (TGFBR1 and TGFBRAP1) mRNA and protein 
      expression. Reporter genes with putative miR-181a binding sites from the TGFBR1 
      and TGFBRAP1 3'-untranslated regions (3'-UTRs) were downregulated in the presence 
      of miR-181a, suggesting that miR-181a binds to TGFBR1 and TGFBRAP1 3'-UTRs. In 
      contrast, transfection of MSCs with miR-181a oligo enhanced expression of IL-6 
      and indoleamine 2,3-dioxygenase by activating p38 and JNK signaling pathways, 
      respectively. MSCs transfected with miR-181a also enhanced the proliferation of T 
      cells in a short-term culture. Additionally, treatment with control MSCs, but not 
      miR-181a transfected MSCs, improved dextran sulfate sodium-induced experimental 
      colitis, suggesting that miR-181a attenuates the immunosuppressive properties of 
      MSCs in vivo. Together, our data demonstrate that miR-181a is an important 
      endogenous regulator in the proliferation and immunosuppressive properties of 
      MSCs.
CI  - Copyright (c) 2012 AlphaMed Press.
FAU - Liu, Liu
AU  - Liu L
AD  - Immunology and Reproductive Biology Lab, Medical School & State Key Laboratory of 
      Pharmaceutical Biotechnology, Nanjing University, Nanjing, People's Republic of 
      China.
FAU - Wang, Yaping
AU  - Wang Y
FAU - Fan, Hongye
AU  - Fan H
FAU - Zhao, Xiaoyin
AU  - Zhao X
FAU - Liu, Dan
AU  - Liu D
FAU - Hu, Yali
AU  - Hu Y
FAU - Kidd, Ambrose R 3rd
AU  - Kidd AR 3rd
FAU - Bao, Jianxin
AU  - Bao J
FAU - Hou, Yayi
AU  - Hou Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Stem Cells
JT  - Stem cells (Dayton, Ohio)
JID - 9304532
RN  - 0 (Interleukin-6)
RN  - 0 (MIrn181 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Transforming Growth Factor beta)
SB  - IM
MH  - Animals
MH  - Cell Growth Processes/immunology
MH  - Disease Models, Animal
MH  - Humans
MH  - Interleukin-6/immunology
MH  - Mesenchymal Stem Cells/cytology/*immunology
MH  - Mice
MH  - MicroRNAs/genetics/*immunology
MH  - Transfection
MH  - Transforming Growth Factor beta/immunology
EDAT- 2012/06/21 06:00
MHDA- 2013/03/01 06:00
CRDT- 2012/06/21 06:00
PHST- 2012/06/21 06:00 [entrez]
PHST- 2012/06/21 06:00 [pubmed]
PHST- 2013/03/01 06:00 [medline]
AID - 10.1002/stem.1156 [doi]
PST - ppublish
SO  - Stem Cells. 2012 Aug;30(8):1756-70. doi: 10.1002/stem.1156.