PMID- 25875646
OWN - NLM
STAT- MEDLINE
DCOM- 20160113
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 4
DP  - 2015
TI  - Down-regulation of microRNA-223 promotes degranulation via the PI3K/Akt pathway 
      by targeting IGF-1R in mast cells.
PG  - e0123575
LID - 10.1371/journal.pone.0123575 [doi]
LID - e0123575
AB  - BACKGROUND: Mast cells play a central role in allergic and inflammatory disorders 
      by inducing degranulation and inflammatory mediator release. Recent reports have 
      shown that miRNAs play an important role in inflammatory response regulation. 
      Therefore, the role of miR-223 in mast cells was investigated. METHODS: The 
      expression of miR-223 was quantified by quantitative real-time polymerase chain 
      reaction (qRT-PCR) in immunoglobulin E (IgE)-mediated mast cells. After 
      successful miR-223 inhibition by transfection, degranulation was detected in 
      IgE-mediated mast cells. The phosphorylation of IkappaB-alpha and Akt were examined using 
      western blotting. NF-kappaB was tested using electrophoretic mobility shift assay. 
      PI3K-inhibitor (LY294002) was used to investigate whether the PI3K/Akt pathway 
      was essential for mast cell activation. The TargetScan database and a luciferase 
      reporter system were used to identify whether insulin-like growth factor 1 
      receptor (IGF-1R) is a direct target of miR-223. RESULTS: MiR-223 expression was 
      up-regulated in IgE-mediated mast cells, whereas its down-regulation promoted 
      mast cell degranulation. Levels of IkappaB-alpha and Akt phosphorylation as well as NF-kappaB 
      were increased in miR-223 inhibitor cells. LY294002 could block the PI3K/Akt 
      signaling pathway and rescue the promotion caused by suppressing miR-223 in mast 
      cells. IGF-1R was identified as a direct target of miR-223. CONCLUSIONS: These 
      findings suggest that down-regulation of miR-223 promotes degranulation via the 
      PI3K/Akt pathway by targeting IGF-1R in mast cells.
FAU - Wang, Quan
AU  - Wang Q
AD  - Department of Respiratory Medicine, Nanjing Children's Hospital Affiliated to 
      Nanjing Medical University, Nanjing, China.
FAU - Zhao, De-Yu
AU  - Zhao DY
AD  - Department of Respiratory Medicine, Nanjing Children's Hospital Affiliated to 
      Nanjing Medical University, Nanjing, China.
FAU - Xu, Hong
AU  - Xu H
AD  - Department of Respiratory Medicine, Nanjing Children's Hospital Affiliated to 
      Nanjing Medical University, Nanjing, China.
FAU - Zhou, Hui
AU  - Zhou H
AD  - Department of Pediatrics, Nanjing Maternal and Child Health Hospital of Nanjing 
      Medical University, Nanjing, China.
FAU - Yang, Qian-Yuan
AU  - Yang QY
AD  - Department of Respiratory Medicine, Nanjing Children's Hospital Affiliated to 
      Nanjing Medical University, Nanjing, China.
FAU - Liu, Feng
AU  - Liu F
AD  - Department of Respiratory Medicine, Nanjing Children's Hospital Affiliated to 
      Nanjing Medical University, Nanjing, China.
FAU - Zhou, Guo-Ping
AU  - Zhou GP
AD  - Department of Pediatrics, the Frist Affiliated Hospital of Nanjing Medical 
      University, Nanjing, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150413
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Chromones)
RN  - 0 (MicroRNAs)
RN  - 0 (Morpholines)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - *Cell Degranulation/drug effects
MH  - Cell Line
MH  - Chromones/pharmacology
MH  - *Down-Regulation/drug effects
MH  - Immunoglobulin E/metabolism
MH  - Mast Cells/drug effects/enzymology/*physiology
MH  - MicroRNAs/*metabolism
MH  - Morpholines/pharmacology
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Rats
MH  - Receptor, IGF Type 1/*metabolism
MH  - Signal Transduction/drug effects
MH  - Up-Regulation
PMC - PMC4395227
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/04/16 06:00
MHDA- 2016/01/14 06:00
PMCR- 2015/04/13
CRDT- 2015/04/16 06:00
PHST- 2014/12/13 00:00 [received]
PHST- 2015/03/05 00:00 [accepted]
PHST- 2015/04/16 06:00 [entrez]
PHST- 2015/04/16 06:00 [pubmed]
PHST- 2016/01/14 06:00 [medline]
PHST- 2015/04/13 00:00 [pmc-release]
AID - PONE-D-14-55993 [pii]
AID - 10.1371/journal.pone.0123575 [doi]
PST - epublish
SO  - PLoS One. 2015 Apr 13;10(4):e0123575. doi: 10.1371/journal.pone.0123575. 
      eCollection 2015.