Activation of protease-activated receptor 2 induces VEGF independently of HIF-1.

<h4>Background</h4>Human adipose stem cells (hASCs) can promote angiogenesis through secretion of proangiogenic factors such as vascular endothelial growth factor (VEGF). In other cell types, it has been shown that induction of VEGF is mediated by both protease activated receptor 2 (PAR2...

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Autores principales:	Jeppe Grøndahl Rasmussen, Simone Elkjær Riis, Ole Frøbert, Sufang Yang, Jens Kastrup, Vladimir Zachar, Ulf Simonsen, Trine Fink
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2c5501db39ae4db18f2c8bcdc7d8a4d9
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spelling	oai:doaj.org-article:2c5501db39ae4db18f2c8bcdc7d8a4d92021-11-18T08:14:04ZActivation of protease-activated receptor 2 induces VEGF independently of HIF-1.1932-620310.1371/journal.pone.0046087https://doaj.org/article/2c5501db39ae4db18f2c8bcdc7d8a4d92012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23049945/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Human adipose stem cells (hASCs) can promote angiogenesis through secretion of proangiogenic factors such as vascular endothelial growth factor (VEGF). In other cell types, it has been shown that induction of VEGF is mediated by both protease activated receptor 2 (PAR2) and hypoxia inducible factor 1(HIF-1). The present study hypothesized that PAR2 stimulation through activation of kinase signaling cascades lead to induction of HIF-1 and secretion of VEGF.<h4>Methodology/principal findings</h4>Immunohistochemistry revealed the expression of PAR2 receptors on the surface of hASCs. Blocking the PAR2 receptors with a specific antibody prior to trypsin treatment showed these receptors are involved in trypsin-evoked increase in VEGF secretion from hASCs. Blocking with specific kinase inhibitors suggested that that activation of MEK/ERK and PI3-kinase/Akt pathways are involved in trypsin-eveoked induction of VEGF. The effect of the trypsin treatment on the transcription of VEGF peaked at 6 hours after the treatment and was comparable to the activation observed after keeping hASCs for 24 hours at 1% oxygen. In contrast to hypoxia, trypsin alone failed to induce HIF-1 measured with ELISA, while the combination of trypsin and hypoxia had an additive effect on both VEGF transcription and secretion, results which were confirmed by Western blot.<h4>Conclusion</h4>In hASCs trypsin and hypoxia induce VEGF expression through separate pathways.Jeppe Grøndahl RasmussenSimone Elkjær RiisOle FrøbertSufang YangJens KastrupVladimir ZacharUlf SimonsenTrine FinkPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e46087 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jeppe Grøndahl Rasmussen Simone Elkjær Riis Ole Frøbert Sufang Yang Jens Kastrup Vladimir Zachar Ulf Simonsen Trine Fink Activation of protease-activated receptor 2 induces VEGF independently of HIF-1.
description	<h4>Background</h4>Human adipose stem cells (hASCs) can promote angiogenesis through secretion of proangiogenic factors such as vascular endothelial growth factor (VEGF). In other cell types, it has been shown that induction of VEGF is mediated by both protease activated receptor 2 (PAR2) and hypoxia inducible factor 1(HIF-1). The present study hypothesized that PAR2 stimulation through activation of kinase signaling cascades lead to induction of HIF-1 and secretion of VEGF.<h4>Methodology/principal findings</h4>Immunohistochemistry revealed the expression of PAR2 receptors on the surface of hASCs. Blocking the PAR2 receptors with a specific antibody prior to trypsin treatment showed these receptors are involved in trypsin-evoked increase in VEGF secretion from hASCs. Blocking with specific kinase inhibitors suggested that that activation of MEK/ERK and PI3-kinase/Akt pathways are involved in trypsin-eveoked induction of VEGF. The effect of the trypsin treatment on the transcription of VEGF peaked at 6 hours after the treatment and was comparable to the activation observed after keeping hASCs for 24 hours at 1% oxygen. In contrast to hypoxia, trypsin alone failed to induce HIF-1 measured with ELISA, while the combination of trypsin and hypoxia had an additive effect on both VEGF transcription and secretion, results which were confirmed by Western blot.<h4>Conclusion</h4>In hASCs trypsin and hypoxia induce VEGF expression through separate pathways.
format	article
author	Jeppe Grøndahl Rasmussen Simone Elkjær Riis Ole Frøbert Sufang Yang Jens Kastrup Vladimir Zachar Ulf Simonsen Trine Fink
author_facet	Jeppe Grøndahl Rasmussen Simone Elkjær Riis Ole Frøbert Sufang Yang Jens Kastrup Vladimir Zachar Ulf Simonsen Trine Fink
author_sort	Jeppe Grøndahl Rasmussen
title	Activation of protease-activated receptor 2 induces VEGF independently of HIF-1.
title_short	Activation of protease-activated receptor 2 induces VEGF independently of HIF-1.
title_full	Activation of protease-activated receptor 2 induces VEGF independently of HIF-1.
title_fullStr	Activation of protease-activated receptor 2 induces VEGF independently of HIF-1.
title_full_unstemmed	Activation of protease-activated receptor 2 induces VEGF independently of HIF-1.
title_sort	activation of protease-activated receptor 2 induces vegf independently of hif-1.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/2c5501db39ae4db18f2c8bcdc7d8a4d9
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Activation of protease-activated receptor 2 induces VEGF independently of HIF-1.

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