title: Suppression of Nestin reveals a critical role for p38-EGFR pathway in neural progenitor cell proliferation.
abstract: The expression of intermediate filament Nestin is necessary for the neural progenitor cells (NPCs) to maintain stemness, but the underlying cellular and molecular mechanism remains unclear. In this study, we demonstrated that Nestin is required for the self-renew of NPCs through activating MAPK and EGFR pathways. Knockdown of Nestin by shRNA inhibited cell cycle progression and proliferation in mouse NPCs. Moreover, suppression of Nestin reduced expression of the epidermal growth factor receptor (EGFR) in NPCs and inhibited the mitogenic effects of EGF on these cells. Treatment of NPCs with p38-MAPK inhibitor PD169316 reversed cell cycle arrest caused by the knockdown of Nestin. Our findings indicate that Nestin promotes NPC proliferation via p38-MAPK and EGFR pathways, and reveals the necessity of these pathways in NPCs self-renewal.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Shang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Wenhan
authors.initials: W
authors.lastname: Yin
authors.affiliation: Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.|Beijing Lab for Cardiovascular Precision Medicine, Capital Medical University, Beijing, China.|The Key Laboratory of Remodeling-Related Cardiovascular Disease, Ministry of Education, Beijing, China.|Beijing Collaborative Innovation Center for Cardiovascular Disorders, Anzhen Hospital, Capital Medical University, Beijing, China.|Deparment of Radiological Medicine, Chongqing Medical University, Chongqing, China.
authors.forename: Xujie
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Cell Biology Peking University Health Science Center, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Dong
authors.affiliation: Deparment of Radiology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Chiu
authors.affiliation: Department of Cell Biology Peking University Health Science Center, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.affiliation: Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.|Beijing Lab for Cardiovascular Precision Medicine, Capital Medical University, Beijing, China.|The Key Laboratory of Remodeling-Related Cardiovascular Disease, Ministry of Education, Beijing, China.|Beijing Collaborative Innovation Center for Cardiovascular Disorders, Anzhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Lu
authors.affiliation: Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.|Beijing Lab for Cardiovascular Precision Medicine, Capital Medical University, Beijing, China.|The Key Laboratory of Remodeling-Related Cardiovascular Disease, Ministry of Education, Beijing, China.|Beijing Collaborative Innovation Center for Cardiovascular Disorders, Anzhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Lan
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints; D002454:Cell Differentiation; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000502:physiology*; D007093:Imidazoles / Q000494:pharmacology; D051379:Mice; D064231:Nestin / Q000037:antagonists & inhibitors / Q000502:physiology*; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
chemical_list: D007093:Imidazoles; D064231:Nestin; D034741:RNA, Small Interfering; D066246:ErbB Receptors; D048051:p38 Mitogen-Activated Protein Kinases; C408604:2-(4-nitrophenyl)-4-(4-fluorophenyl)-5-(4-pyridinyl)-1H-imidazole
keywords: EGFR; NPCs; nestin; proliferation; self-renewal