PMID- 29196658
OWN - NLM
STAT- MEDLINE
DCOM- 20190705
LR  - 20190705
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Dec 1
TI  - Estrogen receptor 1 (ESR1) regulates VEGFA in adipose tissue.
PG  - 16716
LID - 10.1038/s41598-017-16686-7 [doi]
LID - 16716
AB  - 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.
FAU - Fatima, L A
AU  - Fatima LA
AD  - Department of Physiology and Biophysics, Institute of Biomedical Sciences, 
      University of Sao Paulo, Sao Paulo, Brazil. lubiologia2000@yahoo.com.br.
AD  - Biomedical Research Department, Diabetes and Obesity Research Division, 
      Cedars-Sinai Medical Center, Los Angeles, California, USA. 
      lubiologia2000@yahoo.com.br.
FAU - Campello, R S
AU  - Campello RS
AD  - Department of Physiology and Biophysics, Institute of Biomedical Sciences, 
      University of Sao Paulo, Sao Paulo, Brazil.
FAU - Santos, R de Souza
AU  - Santos RS
AD  - Biomedical Research Department, Diabetes and Obesity Research Division, 
      Cedars-Sinai Medical Center, Los Angeles, California, USA.
FAU - Freitas, H S
AU  - Freitas HS
AD  - Department of Physiology and Biophysics, Institute of Biomedical Sciences, 
      University of Sao Paulo, Sao Paulo, Brazil.
FAU - Frank, A P
AU  - Frank AP
AD  - Biomedical Research Department, Diabetes and Obesity Research Division, 
      Cedars-Sinai Medical Center, Los Angeles, California, USA.
FAU - Machado, U F
AU  - Machado UF
AD  - Department of Physiology and Biophysics, Institute of Biomedical Sciences, 
      University of Sao Paulo, Sao Paulo, Brazil.
FAU - Clegg, D J
AU  - Clegg DJ
AD  - Biomedical Research Department, Diabetes and Obesity Research Division, 
      Cedars-Sinai Medical Center, Los Angeles, California, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171201
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 4TI98Z838E (Estradiol)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipocytes/cytology/drug effects/metabolism
MH  - Adipose Tissue, White/drug effects/metabolism
MH  - Animals
MH  - Estradiol/pharmacology
MH  - Estrogen Receptor alpha/antagonists & inhibitors/genetics/*metabolism
MH  - Estrogen Receptor beta/genetics/metabolism
MH  - Female
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/chemistry/metabolism
MH  - Mice
MH  - Promoter Regions, Genetic
MH  - Protein Binding
MH  - RNA Interference
MH  - RNA, Small Interfering/metabolism
MH  - Up-Regulation/drug effects
MH  - Vascular Endothelial Growth Factor A/genetics/*metabolism
PMC - PMC5711936
COIS- The authors declare that they have no competing interests.
EDAT- 2017/12/03 06:00
MHDA- 2019/07/06 06:00
PMCR- 2017/12/01
CRDT- 2017/12/03 06:00
PHST- 2017/09/06 00:00 [received]
PHST- 2017/11/15 00:00 [accepted]
PHST- 2017/12/03 06:00 [entrez]
PHST- 2017/12/03 06:00 [pubmed]
PHST- 2019/07/06 06:00 [medline]
PHST- 2017/12/01 00:00 [pmc-release]
AID - 10.1038/s41598-017-16686-7 [pii]
AID - 16686 [pii]
AID - 10.1038/s41598-017-16686-7 [doi]
PST - epublish
SO  - Sci Rep. 2017 Dec 1;7(1):16716. doi: 10.1038/s41598-017-16686-7.