Different epidermal growth factor receptor signaling pathways in neurons and astrocytes activated by extracellular matrix after spinal cord injury. (October 2019)

• Record Type: Journal Article
• Authors: Zhao, Xin; Li, Zexiong; Liang, Shanshan; Li, Shuai; Ren, Jiaan; Li, Baoman; Zhu, Yue; Xia, Maosheng
• Is Part Of: Neurochemistry international. Volume 129(2019)
• Publication Date: 2019-10
• Subjects: Integrin -- ERK -- Extracellular matrix -- Matrix metalloproteinases -- Src; SCI spinal cord injury -- CNS central nervous system -- ECM extracellular matrix -- ERK1/2 extracellular signal-regulated kinases 1/2 -- FACS fluorescence-activated cell sorting -- EGFR epidermal growth factor receptor -- MMPs matrix metalloproteinases -- BSA bovine serum albumin -- PAGE polyacrylamide gel electrophoresis -- ANOVA analysis of variance -- HB-EGF heparin-binding EGF -- FAK focal adhesion kinase -- MAPK mitogen-activated protein kinase -- CSPGs chondroitin sulfate proteoglycans -- Thy-1 thymus cell antigen 1 -- DNQX 6, 7-dinitroquinoxaline-2, 3(1H, 4H)-dione -- APV DL-2-amino-5-phosphonopentanoic acid -- PP1 4-amino-5- (4-methylphenyl)-7-(t-butyl)pyrazolo[3, 4-d]pyrimidine -- U0126 1, 4-diamino-2, 3-dicyano-1, 4-bis[2-aminophenylthio]butadiene -- FN-439 4-aminobenzoyl-Gly-Pro-D-Leu-D-Ala-NH-OH -- PD168393 4-[(3-bromophenyl)amino]-6-acrylamidoquinazoline; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2019.104500
• Languages: English
• ISSNs: 0197-0186

Abstract

Abstract: Spinal cord injury (SCI) is a serious central nervous system (CNS) trauma that results in permanent and severe disability. The extracellular matrix (ECM) can affect the activation of extracellular signal-regulated kinase 1/2 (ERK1/2 ) by interacting with the ERK integrin subunits. In this study, we built a model of SCI with glial fibrillary acidic protein-green fluorescent protein (GFAP-GFP) and thymus cell antigen 1-yellow fluorescent protein-H (Thy1-YFPH) in mice that express specific transgenes in their astrocytes or neurons. Then, we collected spinal cord neurons or astrocytes by fluorescence-activated cell sorting (FACS). In this way, we investigated the SCI-induced phosphorylation of ERK1/2 and epidermal growth factor receptor (EGFR) in neurons and astrocytes, and we discovered that the SCI-induced EGFR signaling pathways differed between neurons and astrocytes. In the present study, we found that the Src-dependent phosphorylation of EGFR induced by SCI occurred only in neurons, not in astrocytes. This phenomenon may be due to the involvement of Thy-1, which promoted the binding between Src and EGFR in neurons after SCI. In addition, the expression of the integrin subunits after SCI differed between neurons and astrocytes. Our present study shows that the EGFR signaling pathway triggered by SCI in neurons differed from the EGFR signaling pathway triggered in astrocytes, a finding that may help to pave the way for clinical trials of therapies that inhibit EGFR signaling pathways after SCI. Graphical abstract: The different signaling pathways of EGFR phosphorylation induced by SCI in neurons and astrocytes. After building the spinal cord injury model, the extracellular matrix (ECM) was enhanced. Then, the ECM could act on the integrin receptors in neurons and astrocytes. In astrocytes, the integrin receptors stimulated the transactivation of EGFR mediated by MMPs, which indicated that the shedding of an agonist of EGFR, such as HB-EGF or Src, was not required during for activation of this pathway. However, in neurons, Thy-1 promoted the binding between Src and EGFR; as a result, the activation of EGFR stimulated by the integrin receptors was partly dependent on Src and MMP. Moreover, the shedding of HB-EGF could act on EGFR in self and nearby cells and cause the phosphorylation of EGFR. In addition, in neurons and astrocytes, the activation of EGFR could stimulate the phosphorylation of ERK1/2, which could regulate the expression of some integrin subunits.Image 1 Highlights: The phosphorylation of ERK was induced by SCI both in neuron and astrocytes. EGFR signal pathways stimulated by SCI were different in neuron and astrocyte. Src evoked by SCI selectively involved in the transactivation of ERK in neurons. SCI selectively elevated the level of integrin α3, α6 and β1 in astrocytes. The increase of integrin α5/β3 totally depended on the activated ERK in neurons.