Satellite glia not DRG neurons constitutively activate EGFR but EGFR inactivation is not correlated with axon regeneration

被引:14
作者
Ahmed, Zubair [1 ]
Read, Martin L. [1 ]
Berry, Martin [1 ]
Logan, Ann [1 ]
机构
[1] Univ Birmingham, Neuropharmacol & Neurobiol Sect, Sch Clin & Expt Med,Coll Med & Dent Sci, Mol Neurosci Grp,Inst Biomed Res W, Birmingham B15 2TT, W Midlands, England
基金
英国生物技术与生命科学研究理事会;
关键词
EGFR; DRGN; Axon/neurite growth; siRNA; DRG satellite glia; GROWTH-FACTOR RECEPTOR; DORSAL-ROOT GANGLION; VASOACTIVE INTESTINAL POLYPEPTIDE; CHONDROITIN SULFATE PROTEOGLYCANS; CENTRAL-NERVOUS-SYSTEM; SPINAL-CORD-INJURY; NEUROPEPTIDE-Y; NEURITE OUTGROWTH; PERIPHERAL AXOTOMY; CNS MYELIN;
D O I
10.1016/j.nbd.2010.04.013
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
To test the possibility that phosphorylated epidermal growth factor receptor (pEGFR) mediates axon growth inhibition, we determined if pEGFR levels were raised in dorsal root ganglia (DRG) after non-regenerating dorsal column (DC) lesions and suppressed in regenerating sciatic nerve (SN) and preconditioning (P) SN + DC lesioned DRG. Levels of EGFR mRNA and protein in DRG were unchanged between control and all injury models. Satellite glia and not DRG neurons (DRGN) constitutively contained pEGFR and, only in PSN + DC rats, were levels significantly reduced in these cells. In vitro, siRNA mediated knockdown of EGFR (siEGFR) mRNA and protein was associated with suppressed RhoA activation, but fibroblast growth factor-2 (FGF2) was a mandatory requirement for DRGN neuritogenesis after addition of inhibitory concentrations of CNS myelin. Thus. EGFR activation in satellite glia was not consistently correlated with DRGN axogenesis and siEGFR reduction of pEGFR with attenuated Rho-GTP signalling did not promote DRGN disinhibited neurite outgrowth without exogenous FGF2 stimulation. Together, these data argue against a direct intra-axonal involvement of pEGFR in axon regeneration. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:292 / 300
页数:9
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