Estrogen receptor 1 (ESR1) regulates VEGFA in adipose tissue

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) regula...

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Bibliographic Details
Published in:Scientific reports 2017-12, Vol.7 (1), p.16716-14, Article 16716
Main Authors: Fatima, L. A., Campello, R. S., Santos, R. de Souza, Freitas, H. S., Frank, A. P, Machado, U. F., Clegg, D. J.
Format: Article
Language:English
Subjects:
13
17β-Estradiol
631/443/319/2723
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Adipose tissue
Angiogenesis
Estrogen receptors
Estrogens
Fibrosis
Humanities and Social Sciences
Hypoxia
Insulin
multidisciplinary
Science
Science (multidisciplinary)
siRNA
Vascular endothelial growth factor
Vascularization
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-16686-7