MAPK/ERK signalling mediates VEGF-induced bone marrow stem cell differentiation into endothelial cell

J. Xu, X. Liu, Y. Jiang, L. Chu, H. Hao, Z. Liua, C. Verfaillie, J. Zweier, K. Gupta, Z. Liu

Research output: Contribution to journalArticle

Abstract

Multi-potent adult progenitor cells (MAPCs) differentiate into endothelial cells (ECs) in the presence of vascular endothelial growth factor (VEGF). The mechanism(s) of VEGF-induced differentiation of MAPCs to ECs are not yet known. We, therefore, examined the role of mitogen-activated protein kinase/extracellular signal-regulated kinase (p42/44-MAPK/ERK1/2) signalling in endothelial differentiation from bone marrow stem cells. We observed that VEGF stimulation of MAPCs for 14 days results in a significant expression of endothelial-specific gene and/or proteins including von Willebrand factor (vWF), vascular endothelial-cadherin (VE-cadherin), VEGF receptor-2 (VEGFR2), and CD31. Up-regulation of EC-specific markers was accompanied by a cobblestone morphology, expression of endothelial nitric oxide synthase (eNOS), and Dil-Ac-LDL uptake, typical for EC morphology and function. VEGF induced a sustained activation of p42 MAPK/ERK, but not that of p44 MAPK/ERK during the course of MAPCs differentiation in a time-dependent manner up to 14 days. VEGF-induced activation of p42 MAPK/ERK also led to the nuclear translocation of MAPK/ERK1/2. Incubation of MAPCs with MAPK/ERK1/2 phosphorylation inhibitor PD98059 blocked the sustained VEGF-induced MAPK/ERK1/2 phosphorylation as well as its nuclear translocation in the differentiating MAPCs. Inhibition of MAPK/ERK1/2 phosphorylation by PD98059 also blocked the expression of EC-specific genes in these cells and their differentiation to ECs. These data suggest that VEGF induces MAPC differentiation into EC via a. MAPK/ERK1/2 signalling pathway-mediated mechanism in vitro.

Original languageEnglish (US)
Pages (from-to)2395-2406
Number of pages12
JournalJournal of Cellular and Molecular Medicine
Volume12
Issue number6A
DOIs
StatePublished - Dec 2008
Externally publishedYes

    Fingerprint

Keywords

  • Differentiation
  • Endothelial cell
  • ERK
  • MAPCs
  • MAPK
  • VEGF

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine

Cite this

Xu, J., Liu, X., Jiang, Y., Chu, L., Hao, H., Liua, Z., Verfaillie, C., Zweier, J., Gupta, K., & Liu, Z. (2008). MAPK/ERK signalling mediates VEGF-induced bone marrow stem cell differentiation into endothelial cell. Journal of Cellular and Molecular Medicine, 12(6A), 2395-2406. https://doi.org/10.1111/j.1582-4934.2008.00266.x