Crosstalk of EGF-directed MAPK signalling pathways and its potential role on EGF-induced cell proliferation and COX-2 expression in human mesenchymal stem cells.
Epidermal growth factor (EGF) promotes proliferation in human mesenchymal stem cells (hMSCs) during in vitro propagation. In this study, we investigated the effects of PI3K/AKT, ERK1/2, P38 and JNK on EGF signalling in hMSCs. The effects of EGF on MAPKs and PI3K/AKT crosstalk were investigated by immunoblotting; cyclooxygenase-2 (COX-2) expression was studied by real-time RT-PCR; and cell proliferation was evaluated by methylthiazolyl tetrazolium bromide assay. Our results showed that EGF immediately activated all four pathways, induced proliferation and increased COX-2 expression. Interestingly, inhibition of PI3K/AKT-enhanced EGF-stimulated ERK1/2 activity, and inhibition of ERK1/2 and JNK reduced AKT phosphorylation. Furthermore, EGF-induced proliferation as well as EGF-augmented COX2 expression was hindered by ERK1/2 and p38 inhibitors. The results of this study provide evidences to be used in extended proliferation of hMSCs for cell therapy.
Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
Abdullah
A
Sabri
Abed-Ali
AA
Ziaee
Seyed Nasser
SN
Ostad
Kamran
K
Alimoghadam
Mohammad Hossein
MH
Ghahremani
D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism; D020239:Receptor Cross-Talk / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism
D004815:Epidermal Growth Factor; D051546:Cyclooxygenase 2; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4