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

Area of Science:

• Cell Biology
• Stem Cell Research
• Molecular Biology

Background:

• Multi-potent adult progenitor cells (MAPCs) can differentiate into various cell types, including endothelial cells (ECs).
• Vascular endothelial growth factor (VEGF) is known to induce EC differentiation, but the underlying molecular mechanisms are not fully understood.
• The mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK1/2) pathway is a critical signaling cascade involved in cellular processes like differentiation.

Purpose of the Study:

• To investigate the role of the MAPK/ERK1/2 signaling pathway in VEGF-induced differentiation of MAPCs into ECs.
• To elucidate the specific molecular events mediated by VEGF signaling during this differentiation process.

Main Methods:

• MAPCs were stimulated with VEGF for 14 days.
• Endothelial-specific gene and protein expression (vWF, VE-cadherin, VEGFR2, CD31, eNOS) were analyzed.
• Cell morphology and function (Dil-Ac-LDL uptake) were assessed.
• MAPK/ERK1/2 activation and nuclear translocation were examined.
• The effect of a MAPK/ERK1/2 inhibitor (PD98059) on differentiation was evaluated.

Main Results:

• VEGF stimulation led to significant expression of EC-specific markers and acquisition of EC morphology and function.
• VEGF induced sustained activation and nuclear translocation of p42 MAPK/ERK1/2 in a time-dependent manner.
• Inhibition of MAPK/ERK1/2 phosphorylation by PD98059 blocked VEGF-induced EC marker expression and differentiation.
• PD98059 also prevented VEGF-induced MAPK/ERK1/2 phosphorylation and nuclear translocation.

Conclusions:

• VEGF induces MAPC differentiation into ECs through a mechanism involving the MAPK/ERK1/2 signaling pathway.
• Sustained activation of p42 MAPK/ERK1/2 and its nuclear translocation are crucial for VEGF-mediated endothelial differentiation of MAPCs in vitro.