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

Abdullah Sabri; Abed-Ali Ziaee; Seyed Nasser Ostad; Kamran Alimoghadam; Mohammad Hossein Ghahremani

doi:10.1002/cbf.1720

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

Cell Biochem Funct. 2011 Jan-Feb;29(1):64-70. doi: 10.1002/cbf.1720.

Authors

Abdullah Sabri¹, Abed-Ali Ziaee, Seyed Nasser Ostad, Kamran Alimoghadam, Mohammad Hossein Ghahremani

Affiliation

¹ Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.

PMID: 21264892
DOI: 10.1002/cbf.1720

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Proliferation / drug effects
Cells, Cultured
Cyclooxygenase 2 / drug effects
Cyclooxygenase 2 / metabolism*
Epidermal Growth Factor / pharmacology*
Extracellular Signal-Regulated MAP Kinases / drug effects
Extracellular Signal-Regulated MAP Kinases / metabolism
Humans
MAP Kinase Kinase 4 / drug effects
MAP Kinase Kinase 4 / metabolism
MAP Kinase Signaling System / drug effects*
Mesenchymal Stem Cells / drug effects*
Mesenchymal Stem Cells / metabolism*
Phosphatidylinositol 3-Kinases / drug effects
Phosphatidylinositol 3-Kinases / metabolism
Phosphorylation / drug effects
Proto-Oncogene Proteins c-akt / drug effects
Proto-Oncogene Proteins c-akt / metabolism
Receptor Cross-Talk / drug effects*
p38 Mitogen-Activated Protein Kinases / drug effects
p38 Mitogen-Activated Protein Kinases / metabolism

Substances

Epidermal Growth Factor
Cyclooxygenase 2
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt
Extracellular Signal-Regulated MAP Kinases
p38 Mitogen-Activated Protein Kinases
MAP Kinase Kinase 4