title: Small molecule induction of neural-like cells from bone marrow-mesenchymal stem cells.
abstract: Bone marrow-derived mesenchymal stem cells (MSCs) have been demonstrated to be able to differentiate into neuron-like cell, but the precise mechanisms controlling this process are unclear. We report here that LY294002, a small molecule inhibitor of PI3K/AKT signal pathway, can inhibit proliferation and promote neuronal differentiation of MSCs after MSCs incubated with LY294002 for 6 and 12 h. RT-PCR results indicated that mRNA expression of α5β1 integrin significantly increased in neuron-like cell from MSCs. Interestingly, neuron-like cells derived by this method adhere much more strongly than MSCs, which was related to the expression of α5β1 integrin and FAK phosphorylation. However, these effects could be attenuated by LiCL or GSK-3β-siRNA. Our results indicate that activation GSK-3β signaling may be involved in MSCs proliferation, differentiation, and adhesion. Furthermore, this study demonstrates that small molecule regulators of PI3K/AKT signaling may be valuable tools for stem cell research aimed at treatment of neurodegenerative disease.
authors.affiliation: Department of Neurology, Second Affiliated Hospital of Nanchang University, Nanchang City, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.forename: Wenfeng
authors.initials: W
authors.lastname: He
authors.forename: Hetao
authors.initials: H
authors.lastname: Bian
authors.forename: Chuan
authors.initials: C
authors.lastname: Liu
authors.forename: Shiyong
authors.initials: S
authors.lastname: Li
mesh_terms: D000818:Animals; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D019938:Cyclin D1 / Q000235:genetics; D019927:Cyclin E / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1 / Q000235:genetics; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics; D000071679:Glycogen Synthase Kinase 3 beta; D039081:Integrin alpha5beta1 / Q000235:genetics; D018021:Lithium Chloride / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C530106:Ccnd1 protein, rat; D002867:Chromones; D019927:Cyclin E; D004791:Enzyme Inhibitors; D039081:Integrin alpha5beta1; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019938:Cyclin D1; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051417:Focal Adhesion Kinase 1; C496052:Ptk2 protein, rat; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride