Vascular endothelial growth factor stimulates endothelial differentiation from mesenchymal stem cells via Rho/myocardin-related transcription factor-A signaling pathway

Mesenchymal stem cells (MSCs) are pluripotent progenitors that can differentiate into a variety of cell types. Vascular endothelial growth factor (VEGF) is one of the major factors of initiating and regulating angiogenesis. It has been reported that VEGF can induce MSCs differentiated into endotheli...

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Bibliographic Details
Published in:The international journal of biochemistry & cell biology 2013-07, Vol.45 (7), p.1447-1456
Main Authors: Wang, Nan, Zhang, Rui, Wang, Shui-Jing, Zhang, Chun-Ling, Mao, Li-Bin, Zhuang, Chun-Yu, Tang, Yan-Yang, Luo, Xue-Gang, Zhou, Hao, Zhang, Tong-Cun
Format: Article
Language:English
Subjects:
ADP Ribose Transferases
Amides
angiogenesis
Animals
Bone Marrow Cells - metabolism
Bones
Botulinum Toxins
Cell Cycle Proteins
Cell Differentiation
Cell Movement
Cells, Cultured
Cellular differentiation
Cysteine-Rich Protein 61 - biosynthesis
Cysteine-Rich Protein 61 - genetics
Endothelial cells
Endothelial Cells - metabolism
Enzyme Inhibitors
Heterogeneous-Nuclear Ribonucleoprotein Group A-B
Humans
Male
Mesenchymal stem cells
Mesenchymal Stem Cells - metabolism
mutation
Myocardin-related transcription factor-A
Neovascularization, Pathologic - metabolism
Promoter Regions, Genetic
Pyridines
Rats
Rats, Sprague-Dawley
rho-Associated Kinases - antagonists & inhibitors
rho-Associated Kinases - metabolism
RhoA
Ribonucleoproteins
Signal Transduction
stem cells
Transcription Factors - antagonists & inhibitors
Transcription Factors - genetics
Transcription Factors - metabolism
Up-Regulation
Vascular Endothelial Growth Factor A - metabolism
vascular endothelial growth factors
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Summary:Mesenchymal stem cells (MSCs) are pluripotent progenitors that can differentiate into a variety of cell types. Vascular endothelial growth factor (VEGF) is one of the major factors of initiating and regulating angiogenesis. It has been reported that VEGF can induce MSCs differentiated into endothelial cells (ECs). However, the mechanism that VEGF-induced MSC differentiation is not completely understood. Here, we showed that VEGF induced human and rat bone marrow-derived MSCs differentiation to ECs. Rho family plays an important role in VEGF-induced endothelial cell migration and angiogenesis. Our results indicated that in MSCs, VEGF activated Rho/ROCK signaling pathway and promoted nuclear translocation of myocardin-related transcription factor-A (MRTF-A), which is controlled by Rho/ROCK signaling. In addition, Rho inhibitor C3 transferase, ROCK inhibitor Y27632 or depletion of endogenous MRTF-A abolished the VEGF-induced differentiation of MSCs into ECs. Furthermore, VEGF also enhanced the expression levels of CYR61/CCN1, as a regulator of vascular development and angiogenesis, and knockdown of endogenous MRTF-A reduced VEGF-induced the upregulation of CYR61/CCN1. Report assays with site-direct mutation analysis of CYR61/CCN1 promoter demonstrated that MRTF-A transactivated CYR61/CCN1 promoter mainly depending on CArG box. In this study, we identify the Rho/MRTF-A signaling pathway as a main actor in controlling VEGF-induced differentiation of human and rat bone marrow-derived MSCs into endothelial cells.
ISSN:1357-2725
1878-5875
DOI:10.1016/j.biocel.2013.04.021