PMID- 29115495
OWN - NLM
STAT- MEDLINE
DCOM- 20180716
LR  - 20211204
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Linking)
VI  - 17
IP  - 1
DP  - 2018 Jan
TI  - PirB inhibits axonal outgrowth via the PI3K/Akt/mTOR signaling pathway.
PG  - 1093-1098
LID - 10.3892/mmr.2017.7930 [doi]
AB  - Accumulating data strongly suggests that leukocyte immunoglobulin like receptor 
      B1 (PirB) inhibits axonal outgrowth. However, the underlying mechanisms remain 
      unclear. In the present study, cortical neurons of newborn mice were cultured 
      with Nogo‑66 (Nogo‑p4; 4 micromol/l; a PirB ligand) together with NEP1‑40 (Nogo 
      inhibitory peptide) and/or anti‑PirB body (50 mg/ml). PirB mRNA and protein was 
      higher in cultured neurons induced by Nogo‑66 compared with untreated cells. 
      Neurite outgrowth assays demonstrated that the inhibitory effects of Nogo‑66 on 
      axonal outgrowth were reversed by anti‑PirB body. Reverse 
      transcription‑quantitative polymerase chain reaction and western blot assays 
      demonstrated that anti‑PirB treatment led to reduced mRNA and protein expression 
      of phosphoinositide 3‑kinase (PI3K), Akt serine/threonine kinase (Akt), 
      mechanistic target of rapamycin kinase (mTOR), myosin IIA and cofilin, which are 
      involved in axonal outgrowth. Furthermore, blockade of the PI3K/Akt/mTOR pathway 
      using a PI3K inhibitor or an mTOR inhibitor diminished the stimulatory effect of 
      anti‑PirB on axonal outgrowth, and the reduced effect of anti‑PirB on factors 
      that were activation by anti‑PirB. In addition, blockade of PI3K/Akt/mTOR 
      enhanced anti‑PirB‑induced gene and protein expression. These results revealed 
      that PirB functions as a potential suppressor in axonal outgrowth via repressing 
      PI3K/Akt/mTOR signaling pathway, and PirB/PI3K/Akt/mTOR may be a novel target for 
      enhancing axonal outgrowth for developing rational therapeutic strategies.
FAU - Bi, Yong-Yan
AU  - Bi YY
AD  - Department of Neurosurgery, Minhang Hospital, Fudan University, Shanghai 201199, 
      P.R. China.
FAU - Quan, Yong
AU  - Quan Y
AD  - Department of Neurosurgery, Minhang Hospital, Fudan University, Shanghai 201199, 
      P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20171031
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Chromones)
RN  - 0 (Morpholines)
RN  - 0 (Nogo Receptor 1)
RN  - 0 (Pirb protein, mouse)
RN  - 0 (Receptors, Immunologic)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Axons/drug effects/*metabolism
MH  - Cells, Cultured
MH  - Chromones/pharmacology
MH  - Mice
MH  - Morpholines/pharmacology
MH  - Neurons/drug effects/metabolism
MH  - Nogo Receptor 1/agonists/metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Receptors, Immunologic/antagonists & inhibitors/*metabolism
MH  - *Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/*metabolism
EDAT- 2017/11/09 06:00
MHDA- 2018/07/17 06:00
CRDT- 2017/11/09 06:00
PHST- 2016/04/17 00:00 [received]
PHST- 2017/09/22 00:00 [accepted]
PHST- 2017/11/09 06:00 [pubmed]
PHST- 2018/07/17 06:00 [medline]
PHST- 2017/11/09 06:00 [entrez]
AID - 10.3892/mmr.2017.7930 [doi]
PST - ppublish
SO  - Mol Med Rep. 2018 Jan;17(1):1093-1098. doi: 10.3892/mmr.2017.7930. Epub 2017 Oct 
      31.