cAMP induces neuronal differentiation of mesenchymal stem cells via activation of extracellular signal-regulated kinase/MAPK.
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.
Kim
Sung-Soo
SS
Department of Anatomy, Ajou University, School of Medicine, Suwon, Korea.
Choi
Jung-Mi
JM
Kim
Ji-Won
JW
Ham
Dong-Sik
DS
Ghil
Sung-Ho
SH
Kim
Moon-Kyu
MK
Kim-Kwon
Yunhee
Y
Hong
Sung-Youl
SY
Ahn
Seung-Cheol
SC
Kim
Seung-Up
SU
Lee
Young-Don
YD
Suh-Kim
Haeyoung
H
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
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