title: Cell Signaling and Differential Protein Expression in Neuronal Differentiation of Bone Marrow Mesenchymal Stem Cells with Hypermethylated Salvador/Warts/Hippo (SWH) Pathway Genes.
abstract: Human mesenchymal stem cells (MSCs) modified by targeting DNA hypermethylation of genes in the Salvador/Warts/Hippo pathway were induced to differentiate into neuronal cells in vitro. The differentiated cells secreted a significant level of brain-derived neurotrophy factor (BDNF) and the expression of BDNF receptor tyrosine receptor kinase B (TrkB) correlated well with the secretion of BDNF. In the differentiating cells, CREB was active after the binding of growth factors to induce phosphorylation of ERK in the MAPK/ERK pathway. Downstream of phosphorylated CREB led to the functional maturation of differentiated cells and secretion of BDNF, which contributed to the sustained expression of pERK and pCREB. In summary, both PI3K/Akt and MAPK/ERK signaling pathways play important roles in the neuronal differentiation of MSCs. The main function of the PI3K/Akt pathway is to maintain cell survival during neural differentiation; whereas the role of the MAPK/ERK pathway is probably to promote the maturation of differentiated MSCs. Further, cellular levels of protein kinase C epsilon type (PKC-ε) and kinesin heavy chain (KIF5B) increased with time of induction, whereas the level of NME/NM23 nucleoside diphosphate kinase 1 (Nm23-H1) decreased during the time course of differentiation. The correlation between PKC-ε and TrkB suggested that there is cross-talk between PKC-ε and the PI3K/Akt signaling pathway.
authors.affiliation: Department of Chemical Engineering, Systems Biology and Tissue Engineering Research Center, National Chung Cheng University, Minhsiung, Chiayi, 621 Taiwan.
authors.forename: Hui-Hung
authors.initials: HH
authors.lastname: Tzeng
authors.affiliation: Department of Chemical Engineering, Systems Biology and Tissue Engineering Research Center, National Chung Cheng University, Minhsiung, Chiayi, 621 Taiwan.
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Hsu
authors.affiliation: Department of Chemical Engineering, Systems Biology and Tissue Engineering Research Center, National Chung Cheng University, Minhsiung, Chiayi, 621 Taiwan.
authors.forename: Ting-Hao
authors.initials: TH
authors.lastname: Chung
authors.affiliation: Department of Chemical Engineering, Systems Biology and Tissue Engineering Research Center, National Chung Cheng University, Minhsiung, Chiayi, 621 Taiwan.
authors.forename: Wen-Chien
authors.initials: WC
authors.lastname: Lee
authors.affiliation: Department of Chemical Engineering, Systems Biology and Tissue Engineering Research Center, National Chung Cheng University, Minhsiung, Chiayi, 621 Taiwan.
authors.forename: Chi-Hsien
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Department of Chemical Engineering, Systems Biology and Tissue Engineering Research Center, National Chung Cheng University, Minhsiung, Chiayi, 621 Taiwan.
authors.forename: Wan-Chen
authors.initials: WC
authors.lastname: Wang
authors.affiliation: Department of Chemical Engineering, Systems Biology and Tissue Engineering Research Center, National Chung Cheng University, Minhsiung, Chiayi, 621 Taiwan.
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Hsiao
authors.affiliation: Department of Life Science, National Chung Cheng University, Minhsiung, Chiayi, 621, Taiwan.
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Leu
authors.affiliation: Department of Chemical Engineering, Systems Biology and Tissue Engineering Research Center, National Chung Cheng University, Minhsiung, Chiayi, 621 Taiwan.
authors.forename: Tzu-Hsien
authors.initials: TH
authors.lastname: Wang
mesh_terms: D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002470:Cell Survival; D019175:DNA Methylation; D005786:Gene Expression Regulation; D000090683:Hippo Signaling Pathway; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018797:Cell Cycle Proteins; C092745:LATS1 protein, human; D017346:Protein Serine-Threonine Kinases