3D matrix‐embedding inhibits cycloheximide‐mediated sensitization to TNF‐alpha‐induced apoptosis of human endothelial cells
| Autor: | Lisa Riesinger, Elazer R. Edelman, Heiko Methe, Michael Saemisch, Markus Nickmann |
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| Přispěvatelé: | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Programmed cell death Integrin Biomedical Engineering Medicine (miscellaneous) Apoptosis Biology Article Biomaterials Focal adhesion 03 medical and health sciences 0302 clinical medicine Humans Cycloheximide Cells Cultured Tumor Necrosis Factor-alpha Endothelial Cells Cell biology Extracellular Matrix Endothelial stem cell Vascular endothelial growth factor A 030104 developmental biology 030220 oncology & carcinogenesis biology.protein Tumor necrosis factor alpha Tyrosine kinase |
| Zdroj: | PMC |
| Popis: | The programmed form of cell death (apoptosis) is essential for normal development of multicellular organisms. Dysregulation of apoptosis has been linked with embryonal death and is involved in the pathophysiology of various diseases. Others and we previously demonstrated endothelial biology being intertwined with biochemical and structural composition of the subendothelial basement membrane. We now demonstrate that a three-dimensional growing environment significantly shields endothelial cells from cytokine-induced apoptosis. Detailed analysis reveals differences in intracellular signaling pathways in naive endothelial cells and cytokine-stimulated endothelial cells when cells are grown within a three-dimensional collagen-based matrix compared to cells grown on two-dimensional tissue culture plates. Main findings are significantly reduced p53 expression and level of p38-phosphorylation in three-dimensional grown endothelial cells. Despite similar concentrations of focal adhesion kinase, three-dimensional matrix-embedded endothelial cells express significantly less tyrosine-phosphorylated focal adhesion kinase. Pretreatment with antibodies against integrin alpha(v)beta(3) partially reversed the protective effect of three-dimensional matrix-embedding on endothelial apoptosis. Our findings provide detailed insights into the mechanisms of endothelial apoptosis with respect to the spatial matrix environment. These results enhance our understanding of endothelial biology and may otherwise help in the design of tissue-engineered materials. Furthermore, findings on focal adhesion kinase phosphorylation might enhance our understanding of clinical studies with tyrosine kinase inhibitors. |
| Databáze: | OpenAIRE |
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