PirB inhibits axonal outgrowth via the PI3K/Akt/mTOR signaling pathway

Bi,Yong‑Yan; Quan,Yong

doi:10.3892/mmr.2017.7930

PirB inhibits axonal outgrowth via the PI3K/Akt/mTOR signaling pathway

Authors:
- Yong‑Yan Bi
- Yong Quan
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Affiliations: Department of Neurosurgery, Minhang Hospital, Fudan University, Shanghai 201199, P.R. China
Published online on: October 31, 2017 https://doi.org/10.3892/mmr.2017.7930
Pages: 1093-1098

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Abstract

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 µmol/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.

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