The shear stress-induced transcription factor KLF2 affects dynamics and angiopoietin-2 content of Weibel-Palade bodies.
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 a...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3371018?pdf=render |
| _version_ | 1818017816866979840 |
|---|---|
| author | Ellen L van Agtmaal Ruben Bierings Bieuwke S Dragt Thomas A Leyen Mar Fernandez-Borja Anton J G Horrevoets Jan Voorberg |
| author_facet | Ellen L van Agtmaal Ruben Bierings Bieuwke S Dragt Thomas A Leyen Mar Fernandez-Borja Anton J G Horrevoets Jan Voorberg |
| author_sort | Ellen L van Agtmaal |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T07:31:45Z |
| format | Article |
| id | doaj.art-28dce1412ae44a3c8a2dd2d387ab2c3f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-14T07:31:45Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-28dce1412ae44a3c8a2dd2d387ab2c3f2022-12-22T02:05:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0176e3839910.1371/journal.pone.0038399The shear stress-induced transcription factor KLF2 affects dynamics and angiopoietin-2 content of Weibel-Palade bodies.Ellen L van AgtmaalRuben BieringsBieuwke S DragtThomas A LeyenMar Fernandez-BorjaAnton J G HorrevoetsJan VoorbergBACKGROUND: 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.http://europepmc.org/articles/PMC3371018?pdf=render |
| spellingShingle | Ellen L van Agtmaal Ruben Bierings Bieuwke S Dragt Thomas A Leyen Mar Fernandez-Borja Anton J G Horrevoets Jan Voorberg The shear stress-induced transcription factor KLF2 affects dynamics and angiopoietin-2 content of Weibel-Palade bodies. PLoS ONE |
| title | The shear stress-induced transcription factor KLF2 affects dynamics and angiopoietin-2 content of Weibel-Palade bodies. |
| title_full | The shear stress-induced transcription factor KLF2 affects dynamics and angiopoietin-2 content of Weibel-Palade bodies. |
| title_fullStr | The shear stress-induced transcription factor KLF2 affects dynamics and angiopoietin-2 content of Weibel-Palade bodies. |
| title_full_unstemmed | The shear stress-induced transcription factor KLF2 affects dynamics and angiopoietin-2 content of Weibel-Palade bodies. |
| title_short | The shear stress-induced transcription factor KLF2 affects dynamics and angiopoietin-2 content of Weibel-Palade bodies. |
| title_sort | shear stress induced transcription factor klf2 affects dynamics and angiopoietin 2 content of weibel palade bodies |
| url | http://europepmc.org/articles/PMC3371018?pdf=render |
| work_keys_str_mv | AT ellenlvanagtmaal theshearstressinducedtranscriptionfactorklf2affectsdynamicsandangiopoietin2contentofweibelpaladebodies AT rubenbierings theshearstressinducedtranscriptionfactorklf2affectsdynamicsandangiopoietin2contentofweibelpaladebodies AT bieuwkesdragt theshearstressinducedtranscriptionfactorklf2affectsdynamicsandangiopoietin2contentofweibelpaladebodies AT thomasaleyen theshearstressinducedtranscriptionfactorklf2affectsdynamicsandangiopoietin2contentofweibelpaladebodies AT marfernandezborja theshearstressinducedtranscriptionfactorklf2affectsdynamicsandangiopoietin2contentofweibelpaladebodies AT antonjghorrevoets theshearstressinducedtranscriptionfactorklf2affectsdynamicsandangiopoietin2contentofweibelpaladebodies AT janvoorberg theshearstressinducedtranscriptionfactorklf2affectsdynamicsandangiopoietin2contentofweibelpaladebodies AT ellenlvanagtmaal shearstressinducedtranscriptionfactorklf2affectsdynamicsandangiopoietin2contentofweibelpaladebodies AT rubenbierings shearstressinducedtranscriptionfactorklf2affectsdynamicsandangiopoietin2contentofweibelpaladebodies AT bieuwkesdragt shearstressinducedtranscriptionfactorklf2affectsdynamicsandangiopoietin2contentofweibelpaladebodies AT thomasaleyen shearstressinducedtranscriptionfactorklf2affectsdynamicsandangiopoietin2contentofweibelpaladebodies AT marfernandezborja shearstressinducedtranscriptionfactorklf2affectsdynamicsandangiopoietin2contentofweibelpaladebodies AT antonjghorrevoets shearstressinducedtranscriptionfactorklf2affectsdynamicsandangiopoietin2contentofweibelpaladebodies AT janvoorberg shearstressinducedtranscriptionfactorklf2affectsdynamicsandangiopoietin2contentofweibelpaladebodies |