Embryonic stem cells utilize reactive oxygen species as transducers of mechanical strain-induced cardiovascular differentiation
| Autor: | Maike Schmelter, Bernadette Ateghang, Simone Helmig, Maria Wartenberg, Heinrich Sauer |
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| Rok vydání: | 2006 |
| Předmět: |
Vascular Endothelial Growth Factor A
Angiogenesis p38 mitogen-activated protein kinases Cellular differentiation Biochemistry chemistry.chemical_compound Mice Vasculogenesis Genetics Animals Myocytes Cardiac Molecular Biology NADPH oxidase biology MEF2 Transcription Factors Stem Cells NADPH Oxidases Cell Differentiation Free Radical Scavengers Embryo Mammalian Hypoxia-Inducible Factor 1 alpha Subunit Cell biology GATA4 Transcription Factor Vascular endothelial growth factor Vascular endothelial growth factor A chemistry Myogenic Regulatory Factors biology.protein Stress Mechanical Stem cell Mitogen-Activated Protein Kinases Reactive Oxygen Species Biotechnology |
| Zdroj: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 20(8) |
| ISSN: | 1530-6860 |
| Popis: | Growing stem cells are subjected to mechanical forces, which may initiate differentiation programs. Mechanical strain stimulated cardiovascular differentiation of mouse embryonic stem (ES) cells as evaluated by quantification of contracting cardiac foci and capillary areas, respectively. Mechanical strain rapidly elevated intracellular reactive oxygen species (ROS). After 24 h up-regulation of NADPH oxidase subunits p22-phox, p47-phox, p67-phox, and Nox-4 as well as Nox-1 and Nox-4 mRNA was observed. In parallel, mechanical strain increased hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) mRNA and protein as well as MEF2C and GATA-4 mRNA, which are involved in cardiovascular development. Furthermore, phosphorylation of extracellular-regulated kinase 1,2 (ERK1,2), p38, and c-jun N-terminal kinase (c-Jun NH2-terminal kinase (JNK)) was observed. Stimulation of cardiovascular commitment, HIF-1alpha, VEGF, and MEF2C expression as well as MAPK activation were abolished by free radical scavengers, whereas GATA-4 expression was increased. Cardiomyogenesis was inhibited by the p38 inhibitor SB203580, the ERK1,2 inhibitor UO126, and the JNK inhibitor SP600125. Vasculogenesis/angiogenesis was blunted following inhibition of ERK1,2 and JNK, whereas p38 inhibition was ineffective. Our data outline a role of ROS as mechanotransducing molecules in mechanical strain-stimulated cardiovascular differentiation of ES cells, and point toward a microenvironment of elevated ROS required for signaling cascades initiating cardiovascular differentiation programs. |
| Databáze: | OpenAIRE |
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