Open AccessMAPK/ERK signalling mediates VEGF‐induced bone marrow stem cell differentiation into endothelial cell
Author(s) -
Xu J.,
Liu X.,
Jiang Y.,
Chu L.,
Hao H.,
Liua Z.,
Verfaillie C.,
Zweier J.,
Gupta K.,
Liu Z.
Publication year - 2008
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2008.00266.x
Subject(s) - mapk/erk pathway , microbiology and biotechnology , vascular endothelial growth factor , biology , kinase , endothelial stem cell , protein kinase a , chemistry , cancer research , biochemistry , in vitro , vegf receptors
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.