Saemisch, Michael and Nickmann, Markus and Riesinger, Lisa and Edelman, Elazer R. and Methe, Heiko (2018) 3D matrix-embedding inhibits cycloheximide-mediated sensitization to TNF-alpha-induced apoptosis of human endothelial cells. JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, 12 (4). pp. 1085-1096. ISSN 1932-6254, 1932-7005
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FOCAL ADHESION KINASE; BCL-2 FAMILY PROTEINS; EXTRACELLULAR-MATRIX; CULTURE-SYSTEMS; IN-VITRO; COLLAGEN MATRICES; OXIDIZED LDL; IMPLANTS; ACTIVATION; EXPRESSION; apoptosis; endothelial cell; focal adhesion kinase; integrin; p53; three-dimensional matrix |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 11 Mar 2020 08:03 |
| Last Modified: | 11 Mar 2020 08:03 |
| URI: | https://pred.uni-regensburg.de/id/eprint/14824 |
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