title: cAMP induces neuronal differentiation of mesenchymal stem cells via activation of extracellular signal-regulated kinase/MAPK.
abstract: Mesenchymal stem cells are able to trans-differentiate into nonmesodermal lineage cells. Here, we identified downstream signaling molecules required for acquisition of neuron-like traits by mesenchymal stem cells following the elevation of intracellular cAMP levels. We found that forskolin induced neuron-like morphology and expression of neuron-specific enolase and neurofilament-200 in mesenchymal stem cells. Forskolin sequentially activated protein kinase A and B-regulation of alpha-fetoprotein (Raf), which led to phosphorylation of extracellular signal-regulated kinase. Importantly, blockade of extracellular signal-regulated kinase phosphorylation with a mitogen-activated protein kinase (MAPK) kinase inhibitor abrogated the forskolin-induced morphological changes and induction of neuronal proteins. These results indicate that extracellular signal-regulated kinase/MAPK mediates both cAMP-induced early cytoskeletal rearrangement and the later induction of neuronal markers in mesenchymal stem cells.
authors.affiliation: Department of Anatomy, Ajou University, School of Medicine, Suwon, Korea.
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Kim
authors.forename: Jung-Mi
authors.initials: JM
authors.lastname: Choi
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Dong-Sik
authors.initials: DS
authors.lastname: Ham
authors.forename: Sung-Ho
authors.initials: SH
authors.lastname: Ghil
authors.forename: Moon-Kyu
authors.initials: MK
authors.lastname: Kim
authors.forename: Yunhee
authors.initials: Y
authors.lastname: Kim-Kwon
authors.forename: Sung-Youl
authors.initials: SY
authors.lastname: Hong
authors.forename: Seung-Cheol
authors.initials: SC
authors.lastname: Ahn
authors.forename: Seung-Up
authors.initials: SU
authors.lastname: Kim
authors.forename: Young-Don
authors.initials: YD
authors.lastname: Lee
authors.forename: Haeyoung
authors.initials: H
authors.lastname: Suh-Kim
mesh_terms: D000293:Adolescent; D015153:Blotting, Western / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D002648:Child; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D013997:Time Factors; D048490:raf Kinases / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D005419:Flavonoids; D005576:Colforsin; D000242:Cyclic AMP; D048490:raf Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one