Estrogen receptor 1 (ESR1) regulates VEGFA in adipose tissue

Autor(es)

Fatima, L. A. ^{[1, 2]} ; Campello, R. S. ^[1] ; Santos, R. de Souza ^[2] ; Freitas, H. S. ^[1] ; Frank, A. P. ^[2] ; Machado, U. F. ^[1] ; Clegg, D. J. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo - Brazil

^[2] Cedars Sinai Med Ctr, Diabet & Obes Res Div, Biomed Res Dept, Los Angeles, CA 90048 - USA

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 7, DEC 1 2017.
• Citações Web of Science: 7

Resumo

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. (AU)

• Processo FAPESP: 15/13652-1 - Efeito do silenciamento do gene Esr1 na regulação da expressão do VEGFA e do Slc2a4/GLUT4 em adipócitos.
• Beneficiário: Luciana Alves de Fátima
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 12/04831-1 - Novos moduladores do controle glicêmico e do desenvolvimento de complicações crônicas no Diabetes mellitus: perspectivas preventivas e terapêuticas
• Beneficiário: Ubiratan Fabres Machado
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 13/03343-6 - Papel do estradiol via VEGFA no processo de angiogênese/adipogênese no tecido adiposo
• Beneficiário: Luciana Alves de Fátima
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado