title: Formyl peptide receptors promotes neural differentiation in mouse neural stem cells by ROS generation and regulation of PI3K-AKT signaling.
abstract: This study aimed to determine whether formyl peptide receptors (FPRs) regulated the differentiation of neural stem cells (NSCs). FPRs promote the migration of NSCs both in vitro and in vivo. However, the role of FPRs during differentiation of NSCs is unknown. Analysis by Western blot showed significantly increased expression of FPR1 and FPR2 during differentiation of NSCs. The activation of FPRs promotes NSCs to differentiate into neurons with more primary neurites and branch points and longer neurites per cell. Meanwhile, this activation also inhibits the differentiation of NSC into astrocytes. This bidirectional effect can be inhibited by the FPRs-specific inhibitor. Moreover, it was found that the activation of FPRs increased the generation of reactive oxygen species (ROS) and phosphorylation of AKT in the NSCs, while N-acetylcysteine and LY294002 inhibited the FPRs-stimulated increase in ROS generation and AKT phosphorylation, and blocked the FPRs-stimulated neural differentiation into neurons. Therefore, FPRs-stimulated neural differentiation was mediated via ROS and PI3K-AKT signaling pathways. Collectively, the present findings provided a novel insight into the functional role of FPRs in neurogenesis, with important implications for its potential use as a candidate for treating brain or spinal cord injury.
authors.affiliation: Department of Spine Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Spine Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.
authors.forename: Guan
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Spine Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.
authors.forename: Xingxing
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Spine Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xue
authors.affiliation: Department of Pathology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
authors.forename: Qiaonan
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Spine Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042, China. mingyong_liu@163.com.
authors.forename: Mingyong
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Spine Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042, China. zhaojianhua1964@yahoo.com.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D044042:Receptors, Formyl Peptide / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D002867:Chromones; C469988:Fpr1 protein, mouse; D009025:Morpholines; D017382:Reactive Oxygen Species; D044042:Receptors, Formyl Peptide; C481578:formyl peptide receptor 2, mouse; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D000111:Acetylcysteine