CoChat
Sign Up
Cited by 40Connective Tissue Growth Factor ResearchMenstrual Health and DisordersReproductive System and Pregnancy

Premenstrual Regulation of the Pro-Angiogenic Factor CYR61 in Human Endometrium

Gashaw, Isabella, Stiller, Simone, Böing, Carsten, Kimmig, Rainer, Winterhager, Elke·2008·Endocrinology
DOI 10.1210/en.2007-1568
Open this paper in CoChat — free account

Abstract

The pro-angiogenic factor cysteine-rich protein 61 (CYR61/CCN1) mediates different signals in tumorigenesis, angiogenesis and is involved in the pathogenesis of endometriosis. In this study we investigated the temporal and spatial expression pattern in human endometrium during the menstrual cycle and its possible regulation mechanisms in the premenstrual phase. CYR61 transcript expression showed two distinct periods of elevated levels in the proliferative phase and in menstrual effluents. Because the menstrual breakdown of the functionalis is triggered by cytokines, prostaglandins (PGs), as well as hypoxia, we used a benign endometrial cell line to investigate if CYR61 is regulated by these factors. Hypoxic conditions transiently induced CYR61 mRNA levels and enhanced the secretion of the CYR61 protein into the medium. The hypoxia-inducible factor (HIF) 1alpha mediated this effect on CYR61 as evidenced by dimethyloxalylglycine treatment and by HIF1alpha short interfering RNA. CYR61 mRNA expression was further regulated by IL-1, TNFalpha, PGE2, and PGF2alpha. In addition, TNFalpha and PGE2 elevated significantly CYR61 cellular protein levels in well-oxygenated cells but had only a slight effect on the quantity of secreted protein. Moreover, PGE2 combined with hypoxic conditions increased CYR61 mRNA and protein levels synergistically, whereas the combination with TNFalpha abolished the CYR61 levels induced by hypoxia. Together, the up-regulation of CYR61 by hypoxia via HIF1alpha, TNFalpha, and PGE2 could represent possible mechanisms for the CYR61 increase at the onset of menstruation. The opposite effect of TNFalpha combined with hypoxia on CYR61 up-regulation could contribute to a balanced expression level of this angiogenic factor in the endometrium.

Integrity signals

Registry

Crossref · 10.1210/en.2007-1568

Cites

47 of 47 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • CCN1 is activated by agonists of G protein-coupled receptors such as thrombin, prostaglandins E2 and F2α, and sphingosine-1-phosphate.

    “CCN1 is activated by agonists of G protein-coupled receptors (GPCRs) such as thrombin [34,35], prostaglandins E2 and F2α [33,36], and sphinogosine-1-phosphate [37].”

    From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [33]

  • CCN1 is induced by bacterial and viral infections and by inflammatory cytokines such as IL-1 and TNF-α.

    “CCN1 is also induced by bacterial and viral infections [29–32], and by inflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor α (TNF-α) [33].”

    From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [33]

  • The angiogenic activities of CCN1 may contribute to its role in the pathogenesis of endometriosis.

    “It is believed that the angiogenic activities of CCN1 may contribute to its role in the pathogenesis of endometriosis [33].”

    From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [33]

  • CCN1 is upregulated in eutopic and ectopic endometria of women with endometriosis.

    “Additionally, CCN1 is upregulated in eutopic and ectopic endometria of women with endometriosis [33]”

    From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [33]

  • CCN1 expression is induced by inflammatory cytokines such as IL-1 and TNF-α.

    “CCN1 expression is induced by inflammatory cytokines such as IL-1 and TNF-α [33,131], as well as by bacterial and viral infections [29–32].”

    From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [33]

Cites

Flagged first, then by citations

4 of the 51 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Related

Authors
Gashaw, I., Stiller, S., Böing, C., Kimmig, R., & Winterhager, E.
Affiliations
  • University of Duisburg-Essen (DE)
  • Department of Obstetrics and Gynaecology (C.B., R.K.), University of Duisburg-Essen, 45122 Essen, Germany
ORCID
Venue
Endocrinology
Publisher
The Endocrine Society
Published
2008-01-17
Volume
149
Issue
5
Pages
2261-2269
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
DOI
10.1210/en.2007-1568
OpenAlex
W2018058518
Cited by
40
References
51
Citations by year
2025: 1 · 2024: 1 · 2022: 3 · 2021: 4 · 2020: 3 · 2017: 1 · 2016: 5 · 2015: 3 · 2014: 4 · 2012: 1
FWCI
1.92
Type
journal article
Language
en
Open access
closed
Locations
  • Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Universitätsklinikum Essen
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Menstrual Health and Disorders
  • Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
Keywords
endometrium, menstrual cycle, premenstrual phase, angiogenesis, hypoxia, HIF-1α, prostaglandins, prostaglandin E2, TNF-α, interleukin-1, cytokine regulation, endometriosis
MeSH terms
Adolescent, Adult, Cells, Cultured, Endometrium, Female, Gene Expression Regulation, Humans, Menstrual Cycle, Middle Aged, RNA, Messenger, Tumor Necrosis Factor-alpha, Dinoprostone, Cohort Studies, Cell Hypoxia, Cytokines, Immediate-Early Proteins, Neovascularization, Physiologic, Intercellular Signaling Peptides and Proteins, Angiogenesis Inducing Agents, Hypoxia-Inducible Factor 1, alpha Subunit, Cysteine-Rich Protein 61

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review