Estrogen receptor 1 (ESR1) regulates VEGFA in adipose tissue

Abstract Vascular endothelial growth factor A (VEGFA) is a key factor in the regulation of angiogenesis in adipose tissue. Poor vascularization during adipose tissue proliferation causes fibrosis and local inflammation, and is associated with insulin resistance. It is known that 17-beta estradiol (E...

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Autores principales: L. A. Fatima, R. S. Campello, R. de Souza Santos, H. S. Freitas, A. P Frank, U. F. Machado, D. J. Clegg
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Lenguaje:EN
Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/261031c622454aaa8af34e8d7519faa8
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spelling oai:doaj.org-article:261031c622454aaa8af34e8d7519faa82021-12-02T15:05:48ZEstrogen receptor 1 (ESR1) regulates VEGFA in adipose tissue10.1038/s41598-017-16686-72045-2322https://doaj.org/article/261031c622454aaa8af34e8d7519faa82017-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-16686-7https://doaj.org/toc/2045-2322Abstract Vascular endothelial growth factor A (VEGFA) is a key factor in the regulation of angiogenesis in adipose tissue. Poor vascularization during adipose tissue proliferation causes fibrosis and local inflammation, and is associated with insulin resistance. It is known that 17-beta estradiol (E2) regulates adipose tissue function and VEGFA expression in other tissues; however, the ability of E2 to regulate VEGFA in adipose tissue is currently unknown. In this study, we showed that, in 3T3-L1 cells, E2 and the estrogen receptor 1 (ESR1) agonist PPT induced VEGFA expression, while ESR1 antagonist (MPP), and selective knockdown of ESR1 using siRNA decreased VEGFA and prevented the ability of E2 to modulate its expression. Additionally, we found that E2 and PPT induced the binding of hypoxia inducible factor 1 alpha subunit (HIF1A) in the VEGFA gene promoter. We further found that VEGFA expression was lower in inguinal and gonadal white adipose tissues of ESR1 total body knockout female mice compared to wild type mice. In conclusion, our data provide evidence of an important role for E2/ESR1 in modulating adipose tissue VEGFA, which is potentially important to enhance angiogenesis, reduce inflammation and improve adipose tissue function.L. A. FatimaR. S. CampelloR. de Souza SantosH. S. FreitasA. P FrankU. F. MachadoD. J. CleggNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
L. A. Fatima
R. S. Campello
R. de Souza Santos
H. S. Freitas
A. P Frank
U. F. Machado
D. J. Clegg
Estrogen receptor 1 (ESR1) regulates VEGFA in adipose tissue
description Abstract Vascular endothelial growth factor A (VEGFA) is a key factor in the regulation of angiogenesis in adipose tissue. Poor vascularization during adipose tissue proliferation causes fibrosis and local inflammation, and is associated with insulin resistance. It is known that 17-beta estradiol (E2) regulates adipose tissue function and VEGFA expression in other tissues; however, the ability of E2 to regulate VEGFA in adipose tissue is currently unknown. In this study, we showed that, in 3T3-L1 cells, E2 and the estrogen receptor 1 (ESR1) agonist PPT induced VEGFA expression, while ESR1 antagonist (MPP), and selective knockdown of ESR1 using siRNA decreased VEGFA and prevented the ability of E2 to modulate its expression. Additionally, we found that E2 and PPT induced the binding of hypoxia inducible factor 1 alpha subunit (HIF1A) in the VEGFA gene promoter. We further found that VEGFA expression was lower in inguinal and gonadal white adipose tissues of ESR1 total body knockout female mice compared to wild type mice. In conclusion, our data provide evidence of an important role for E2/ESR1 in modulating adipose tissue VEGFA, which is potentially important to enhance angiogenesis, reduce inflammation and improve adipose tissue function.
format article
author L. A. Fatima
R. S. Campello
R. de Souza Santos
H. S. Freitas
A. P Frank
U. F. Machado
D. J. Clegg
author_facet L. A. Fatima
R. S. Campello
R. de Souza Santos
H. S. Freitas
A. P Frank
U. F. Machado
D. J. Clegg
author_sort L. A. Fatima
title Estrogen receptor 1 (ESR1) regulates VEGFA in adipose tissue
title_short Estrogen receptor 1 (ESR1) regulates VEGFA in adipose tissue
title_full Estrogen receptor 1 (ESR1) regulates VEGFA in adipose tissue
title_fullStr Estrogen receptor 1 (ESR1) regulates VEGFA in adipose tissue
title_full_unstemmed Estrogen receptor 1 (ESR1) regulates VEGFA in adipose tissue
title_sort estrogen receptor 1 (esr1) regulates vegfa in adipose tissue
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/261031c622454aaa8af34e8d7519faa8
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