Evidence map›Paper›PMID 36476832›Full record

ArticleJournal of molecular endocrinology2023

ERα/ERβ-directed CBS transcription mediates E2β-stimulated hUAEC H2S production.

Jin Bai, Thomas J Lechuga, Joshua Makhoul, Hao Yan, Carol Major, Afshan Hameed, Dong-Bao Chen

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of molecular endocrinology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.8field-weighted citation impact, top 29% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
  2. Crosstalk Between HHandbook of experimental pharmacology · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Jin BaiDepartment of Obstetrics and Gynecology, University of California, Irvine, California, USA.
Thomas J LechugaDepartment of Biology, San Bernardino Valley College, San Bernardino, California, USA.
Joshua MakhoulDepartment of Obstetrics and Gynecology, University of California, Irvine, California, USA.
Hao YanDepartment of Obstetrics and Gynecology, University of California, Irvine, California, USA.
Carol MajorDepartment of Obstetrics and Gynecology, University of California, Irvine, California, USA.
Afshan HameedDepartment of Obstetrics and Gynecology, University of California, Irvine, California, USA.
Dong-Bao ChenDepartment of Obstetrics and Gynecology, University of California, Irvine, California, USA.ORCID 0000-0002-1067-6018
University of California, Irvine · USSan Bernardino Valley College · US

Funding

Actions of Estrogen on Uterine Artery EndotheliumR01HL070562 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHEN, DONGBAO · 2001 to 2025
$6.3M
H2S and Uterine Vasodilation in Pregnancy and PreeclampsiaR01HD105699 · NICHD · UNIVERSITY OF CALIFORNIA-IRVINE · PI CHEN, DONGBAO · 2021 to 2025
$1.9M
Pregnancy-Dependent Protein Sulfyhydration in Human Uterine ArteryR21HD097498 · NICHD · UNIVERSITY OF CALIFORNIA-IRVINE · PI CHEN, DONGBAO · 2019 to 2020
$425k
NHLBI NIH HHS R01 HL070562NICHD NIH HHS R01 HD105699NICHD NIH HHS R21 HD097498
6 · The paper itself

Abstract

Elevated endogenous estrogens stimulate human uterine artery endothelial cell (hUAEC) hydrogen sulfide (H2S) production by selectively upregulating the expression of H2S synthesizing enzyme cystathionine β-synthase (CBS), but the underlying mechanisms are underdetermined. We hypothesized that CBS transcription mediates estrogen-stimulated pregnancy-dependent hUAEC H2S production. Estradiol-17β (E2β) stimulated CBS but not cystathionine γ-lyase (CSE) expression in pregnant human uterine artery ex vivo, which was attenuated by the estrogen receptor (ER) antagonist ICI 182,780. E2β stimulated CBS mRNA/protein and H2S production in primary hUAEC from nonpregnant and pregnant women, but with greater responses in pregnant state; all were blocked by ICI 182,780. Human CBS promoter contains multiple estrogen-responsive elements (EREs), including one ERE preferentially binding ERα (αERE) and three EREs preferentially binding ERβ (βERE), and one full ERE (α/βERE) and one half ERE (½α/βERE) binding both ERα and ERβ. Luciferase assays using reporter genes driven by human CBS promoter with a series of 5'-deletions identified the α/βEREs binding both ERα and ERβ (α/βERE and ½α/βERE) to be important for baseline and E2β-stimulated CBS promoter activation. E2β stimulated ERα/ERβ heterodimerization by recruiting ERα to α/βEREs and βERE, and ERβ to βERE, α/βEREs, and αERE. ERα or ERβ agonist alone trans-activated CBS promoter, stimulated CBS mRNA/protein and H2S production to levels comparable to that of E2β-stimulated, while ERα or ERβ antagonist alone abrogated E2β-stimulated responses. E2β did not change human CSE promoter activity and CSE mRNA/protein in hUAEC. Altogether, estrogen-stimulated pregnancy-dependent hUAEC H2S production occurs by selectively upregulating CBS expression via ERα/ERβ-directed gene transcription.

Indexed as

Cystathionine beta-SynthaseEstrogen Receptor alphaEstrogen Receptor betaHydrogen SulfideReceptors, EstrogenEndothelial CellsEstradiolEstrogensFemaleFulvestrantHumansPregnancyRNA, MessengerUterine ArteryCystathionine beta-SynthaseEstradiolEstrogen Receptor alphaEstrogen Receptor betaEstrogensFulvestrantHydrogen SulfideReceptors, EstrogenRNA, MessengerCBS transcriptionestrogen receptorestrogensH2S biosynthesispregnancy

Identifiers

PMID36476832
PMCPMC9876575
OpenAlexW4310803278

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.