Evidence map›Paper›PMID 26504199›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Uterine endoplasmic reticulum stress-unfolded protein response regulation of gestational length is caspase-3 and -7-dependent.

Chandrashekara Kyathanahalli, Kenna Organ, Rebecca S Moreci, Prashanth Anamthathmakula, Sonia S Hassan, Steve N Caritis, Pancharatnam Jeyasuria, Jennifer C Condon

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

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
8.6field-weighted citation impact, top 3% 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

20 citing papers in PubMed, 38 citations in OpenAlex.

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  11. The frequency and clinical significance of intra-amniotic inflammation in twin pregnancies with preterm labor and intact membranes.The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians · 2019
    Observational
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  16. Progesterone Receptor Regulation of Uterine Adaptation for Pregnancy.Trends in endocrinology and metabolism: TEM · 2018
    Review
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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

8 authors at 3 institutions in 1 country.

Chandrashekara KyathanahalliDepartment of Obstetrics and Gynecology, School of Medicine, Wayne State University, Detroit, MI 48201; Department of Physiology, School of Medicine, Wayne State University, Detroit, MI 48201;
Kenna OrganDepartment of Obstetrics and Gynecology, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA 15213;
Rebecca S MoreciDepartment of Obstetrics and Gynecology, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA 15213;
Prashanth AnamthathmakulaDepartment of Obstetrics and Gynecology, School of Medicine, Wayne State University, Detroit, MI 48201; Department of Physiology, School of Medicine, Wayne State University, Detroit, MI 48201;
Sonia S HassanDepartment of Obstetrics and Gynecology, School of Medicine, Wayne State University, Detroit, MI 48201; Department of Physiology, School of Medicine, Wayne State University, Detroit, MI 48201; Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892.
Steve N CaritisDepartment of Obstetrics and Gynecology, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA 15213;
Pancharatnam JeyasuriaDepartment of Obstetrics and Gynecology, School of Medicine, Wayne State University, Detroit, MI 48201; Department of Physiology, School of Medicine, Wayne State University, Detroit, MI 48201; Department of Obstetrics and Gynecology, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA 15213; Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892.
Jennifer C CondonDepartment of Obstetrics and Gynecology, School of Medicine, Wayne State University, Detroit, MI 48201; Department of Physiology, School of Medicine, Wayne State University, Detroit, MI 48201; Department of Obstetrics and Gynecology, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA 15213; Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892 jcondon@med.wayne.edu.
Wayne State University · USMagee-Womens Research Institute · USUniversity of Pittsburgh · US

Funding

Caspase-3 Maintains Uterine Quiescence in a PR and NF-Kappa B Dependent MannerR01HD065011 · NICHD · WAYNE STATE UNIVERSITY · PI CONDON, JENNIFER C. · 2010 to 2014
$1.5M
NICHD NIH HHS 1R01 HD065011NICHD NIH HHS R01 HD065011
6 · The paper itself

Abstract

We previously identified myometrial caspase-3 (CASP3) as a potential regulator of uterine quiescence. We also determined that during pregnancy, the functional activation of uterine CASP3 is likely governed by an integrated endoplasmic reticulum stress response (ERSR) and is consequently limited by an increased unfolded protein response (UPR). The present study examined the functional relevance of uterine UPR-ERSR in maintaining myometrial quiescence and regulating the timing of parturition. In vitro analysis of the human uterine myocyte hTERT-HM cell line revealed that tunicamycin (TM)-induced ERSR modified uterine myocyte contractile responsiveness. Accordingly, alteration of in vivo uterine UPR-ERSR using a pregnant mouse model significantly modified gestational length. We determined that "normal" gestational activation of the ERSR-induced CASP3 and caspase 7 (CASP7) maintains uterine quiescence through previously unidentified proteolytic targeting of the gap junction protein, alpha 1(GJA1); however, surprisingly, TM-induced uterine ERSR triggered an exaggerated UPR that eliminated uterine CASP3 and 7 tocolytic action precociously. These events allowed for a premature increase in myometrial GJA1 levels, elevated contractile responsiveness, and the onset of preterm labor. Importantly, a successful reversal of the magnified ERSR-induced preterm birth phenotype could be achieved by pretreatment with 4-phenylbutrate, a chaperone protein mimic.

Indexed as

Analysis of VarianceAnimalsCaspase 3Caspase 7Cell LineDNA PrimersEndoplasmic Reticulum StressEnzyme-Linked Immunosorbent AssayFemaleFluorescent Antibody TechniqueHumansImmunoblottingMiceMyometriumPhenylbutyratesPregnancy4-phenylbutyric acidCaspase 3Caspase 7DNA PrimersPhenylbutyratesProgesteronecaspase-3 and -7endoplasmic reticulum stresspreterm laborunfolded protein responseuterus

Identifiers

PMID26504199
PMCPMC4653163
OpenAlexW1842159282

What OpenQuestion holds

Textmetadata
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.