The shear stress-induced transcription factor KLF2 affects dynamics and angiopoietin-2 content of Weibel-Palade bodies
| Autor: | Jan Voorberg, Ellen L. van Agtmaal, Ruben Bierings, Mar Fernandez-Borja, Thomas A. Leyen, Anton J.G. Horrevoets, Bieuwke S. Dragt |
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| Přispěvatelé: | Molecular cell biology and Immunology, ICaR - Ischemia and repair, Landsteiner Laboratory, Other departments |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Immunology
Immunocytochemistry Cell Kruppel-Like Transcription Factors lcsh:Medicine Stimulation Cardiovascular Bioinformatics Biochemistry Microbiology Vector Biology Angiopoietin-2 Downregulation and upregulation Vascular Biology Stress Physiological Molecular Cell Biology Weibel–Palade body medicine Humans Secretion lcsh:Science Biology Transcription factor Cells Cultured Inflammation Plasma Proteins Multidisciplinary Weibel-Palade Bodies Chemistry lcsh:R Immunity Proteins Endothelial Cells Cellular Structures Cell biology medicine.anatomical_structure Subcellular Organelles Gene Expression Regulation KLF2 Medicine Cytokines lcsh:Q Viral Vectors Cellular Types Shear Strength Coagulation Factors Research Article |
| Zdroj: | PLoS ONE, Vol 7, Iss 6, p e38399 (2012) PLoS ONE, 7(6):e38399. Public Library of Science PLoS ONE PLoS ONE, 7(6). Public Library of Science van Agtmaal, E L, Bierings, R, Dragt, B S, Leyen, T A, Fernandez-Borja, M, Horrevoets, A J G & Voorberg, J 2012, ' The Shear Stress-Induced Transcription Factor KLF2 Affects Dynamics and Angiopoietin-2 Content of Weibel-Palade Bodies ', PLoS ONE, vol. 7, no. 6, e38399 . https://doi.org/10.1371/journal.pone.0038399 |
| ISSN: | 1932-6203 |
| Popis: | BACKGROUND: The shear-stress induced transcription factor KLF2 has been shown to induce an atheroprotective phenotype in endothelial cells (EC) that are exposed to prolonged laminar shear. In this study we characterized the effect of the shear stress-induced transcription factor KLF2 on regulation and composition of Weibel-Palade bodies (WPBs) using peripheral blood derived ECs. METHODOLOGY AND PRINCIPAL FINDINGS: Lentiviral expression of KLF2 resulted in a 4.5 fold increase in the number of WPBs per cell when compared to mock-transduced endothelial cells. Unexpectedly, the average length of WPBs was significantly reduced: in mock-transduced endothelial cells WPBs had an average length of 1.7 µm versus 1.3 µm in KLF2 expressing cells. Expression of KLF2 abolished the perinuclear clustering of WPBs observed following stimulation with cAMP-raising agonists such as epinephrine. Immunocytochemistry revealed that WPBs of KLF2 expressing ECs were positive for IL-6 and IL-8 (after their upregulation with IL-1β) but lacked angiopoietin-2 (Ang2), a regular component of WPBs. Stimulus-induced secretion of Ang2 in KLF2 expressing ECs was greatly reduced and IL-8 secretion was significantly lower. CONCLUSIONS AND SIGNIFICANCE: These data suggest that KLF2 expression leads to a change in size and composition of the regulated secretory compartment of endothelial cells and alters its response to physiological stimuli. |
| Databáze: | OpenAIRE |
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