title: mGluR3 promotes proliferation of human embryonic cortical neural progenitor cells by activating ERK1/2 and JNK2 signaling pathway in vitro.
abstract: Metabotropic glutamate receptors (mGluRs) regulate the proliferation and differentiation of neural progenitor cells (NPCs) in brain; however, the mechanisms remain unknown. In this study, we investigated the effect of mGluR3 on the proliferation of human embryonic neural progenitor cells (NPCs), the expression of cyclin D1 and the activation of signaling pathways of mitogen-activated protein kinases (MAPKs). The results showed that mGluR3 agonist N-Acetylaspartylglutamate (NAAG) increased the proliferation of NPCs by increasing cell activity, diameter of neurospheres and cell division. In addition, mGluR3 siRNA decreased the NPC proliferation. The protein expressions of cyclin D1 increased with NAAG treatment and decreased after siRNA treatment. It was also found that activation of extracellular signal-regulated protein kinase (ERK) and c-Jun N-terminal protein kinase (JNK) signaling pathways were involved in the proliferation of NPCs. NAAG increased phosphorylation of ERK1/2 and JNK2 levels, and meanwhile p-p38 level decreased; but p-ERK1/2 and p-JNK2 levels decreased after siRNA treatment, and p-p38 level increased. ERK1/2 inhibitor U0126 and JNK2 inhibitor SP600125 attenuated the increase of proliferation induced by NAAG. These findings demonstrated that mGluR3 promoted the proliferation of human embryonic cortical NPCs and increased cyclin D1 expression by activating ERK1/2 and JNK2 signaling pathways in vitro, suggesting that mGluR3 may be a target molecule for regulating NPC proliferation in brain development.
authors.affiliation: The Third Affiliated Hospital, School of Medicine, Xi&apos;an Jiaotong University Department of Neurosurgery, Xi&apos;an China.
authors.forename: J
authors.initials: J
authors.lastname: Guo
authors.affiliation: Affiliated Hospital, Medical College of Yan&apos;an University Department of Neurosurgery Yan&apos;an City China.
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Affiliated Hospital, Medical College of Yan&apos;an University Department of Neurosurgery Yan&apos;an City China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Affiliated Hospital, Medical College of Yan&apos;an University Department of Neurosurgery Yan&apos;an City China.
authors.forename: M
authors.initials: M
authors.lastname: Bai
authors.affiliation: Affiliated Hospital, Medical College of Yan&apos;an University Department of Neurosurgery Yan&apos;an City China.
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.affiliation: Affiliated Hospital, Medical College of Yan&apos;an University Department of Neurosurgery Yan&apos;an City China.
authors.forename: K
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Affiliated Hospital, Medical College of Yan&apos;an University Department of Neurosurgery Yan&apos;an City China.
authors.forename: W
authors.initials: W
authors.lastname: Hao
authors.affiliation: Affiliated Hospital, Medical College of Yan&apos;an University Department of Neurosurgery Yan&apos;an City China.
authors.forename: W
authors.initials: W
authors.lastname: Wei
authors.affiliation: The Third Affiliated Hospital, School of Medicine, Xi&apos;an Jiaotong University Department of Neurosurgery, Xi&apos;an China xjtzhangyuelin&commat;126.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D002525:Cerebellar Cortex / Q000166:cytology*; D019938:Cyclin D1 / Q000378:metabolism; D004151:Dipeptides / Q000494:pharmacology; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004151:Dipeptides; D034741:RNA, Small Interfering; D018094:Receptors, Metabotropic Glutamate; C102718:metabotropic glutamate receptor 3; D019938:Cyclin D1; C027172:isospaglumic acid; D048056:Mitogen-Activated Protein Kinase 9; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3