title: Metabotropic glutamate receptor 5 promotes proliferation of human neural stem/progenitor cells with activation of mitogen-activated protein kinases signaling pathway in vitro.
abstract: Metabotropic glutamate receptors (mGluRs) regulate neurogenesis in brain, but the mechanisms remain unknown. In this study, we investigated the effect of mGluR5 on the proliferation of human embryonic neural stem/progenitor cells (NPCs), the expression of cyclin D1 and the activation of signaling pathways of mitogen-activated protein kinases (MAPKs). Results showed that mGluR5 agonist (S)-3,5-dihydroxyphenylglycine hydrate (DHPG) increased the proliferation of NPCs by increasing cell activity, diameter of neurospheres and cell division, while mGluR5 siRNA and antagonist 6-methyl-2-(phenylethynyl) pyridine hydrochloride (MPEP) decreased the NPC proliferation. The mRNA and protein expressions of cyclin D1 increased with DHPG treatment and decreased after siRNA or MPEP 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. After DHPG treatment, p-ERK1/2 and p-JNK2 levels increased, and meanwhile p-p38 level decreased; but p-ERK1/2 and p-JNK2 levels decreased after siRNA or MPEP treatment, and p-p38 level increased. Our findings demonstrated that mGluR5 promoted the proliferation of human embryonic cortical NPCs and increased cyclin D1 expression with the changes in phosphorylation of MAPKs signaling pathways in vitro, suggesting a novel mechanism for pharmacological study of treatment for ischemic brain injury and neurodegenerative disorders.
authors: Institute of Neurobiology, Environment and Genes Related to Diseases Key Laboratory of Education Ministry, Xi'an Jiaotong University College of Medicine, 710061, PR China.
authors: L
authors: L
authors: Zhao
authors: Q
authors: Q
authors: Jiao
authors: P
authors: P
authors: Yang
authors: X
authors: X
authors: Chen
authors: J
authors: J
authors: Zhang
authors: B
authors: B
authors: Zhao
authors: P
authors: P
authors: Zheng
authors: Y
authors: Y
authors: Liu
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation; D002469:Cell Separation; D005434:Flow Cytometry; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D058953:Neural Stem Cells / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*
chemical_list: C578935:GRM5 protein, human; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate