Evidence map›Paper›PMID 19834610›Full record

ArticlePloS one2009

Stretch activates human myometrium via ERK, caldesmon and focal adhesion signaling.

Yunping Li, Maya Reznichenko, Rachel M Tribe, Philip E Hess, Michael Taggart, HakRim Kim, Jon P DeGnore, Samudra Gangopadhyay, Kathleen G Morgan

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

31 citing papers in PubMed, 51 citations in OpenAlex.

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  20. Aging impairs smooth muscle-mediated regulation of aortic stiffness: a defect in shock absorption function?American journal of physiology. Heart and circulatory physiology · 2014
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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

9 authors at 7 institutions in 2 countries.

Yunping LiDepartment of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America. yli1@bidmc.harvard.edu
Maya Reznichenko
Rachel M Tribe
Philip E Hess
Michael Taggart
HakRim Kim
Jon P DeGnore
Samudra Gangopadhyay
Kathleen G Morgan
Boston University · USHarvard University · USBeth Israel Deaconess Medical Center · USBoston Biomedical Research Institute · USKing's College London · GBNewcastle University · GBTufts University · US

Funding

Structure-Function of the CytoskeletonP01HL086655 · NHLBI · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI MORGAN, KATHLEEN G · 2007 to 2011
$8.8M
Subcellular Organization of Signaling in Smooth MuscleR01HL080003 · NHLBI · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI MORGAN, KATHLEEN G · 2006 to 2009
$1.7M
SIGNALING AND UTERINE CONTRACTILITY DURING PREGNANCYR01HD043054 · NICHD · BOSTON BIOMEDICAL RESEARCH INSTITUTE · PI MORGAN, KATHLEEN G · 2003 to 2007
$1.7M
NHLBI NIH HHS HL80003NHLBI NIH HHS HL86655NHLBI NIH HHS P01 HL086655NHLBI NIH HHS R01 HL080003NICHD NIH HHS HD043054NICHD NIH HHS R01 HD043054Wellcome Trust
6 · The paper itself

Abstract

An incomplete understanding of the molecular mechanisms responsible for myometrial activation from the quiescent pregnant state to the active contractile state during labor has hindered the development of effective therapies for preterm labor. Myometrial stretch has been implicated clinically in the initiation of labor and the etiology of preterm labor, but the molecular mechanisms involved in the human have not been determined. We investigated the mechanisms by which gestation-dependent stretch contributes to myometrial activation, by using human uterine samples from gynecologic hysterectomies and Cesarean sections. Here we demonstrate that the Ca requirement for activation of the contractile filaments in human myometrium increases with caldesmon protein content during gestation and that an increase in caldesmon phosphorylation can reverse this inhibitory effect during labor. By using phosphotyrosine screening and mass spectrometry of stretched human myometrial samples, we identify 3 stretch-activated focal adhesion proteins, FAK, p130Cas, and alpha actinin. FAK-Y397, which signals integrin engagement, is constitutively phosphorylated in term human myometrium whereas FAK-Y925, which signals downstream ERK activation, is phosphorylated during stretch. We have recently identified smooth muscle Archvillin (SmAV) as an ERK regulator. A newly produced SmAV-specific antibody demonstrates gestation-specific increases in SmAV protein levels and stretch-specific increases in SmAV association with focal adhesion proteins. Thus, whereas increases in caldesmon levels suppress human myometrium contractility during pregnancy, stretch-dependent focal adhesion signaling, facilitated by the ERK activator SmAV, can contribute to myometrial activation. These results suggest that focal adhesion proteins may present new targets for drug discovery programs aimed at regulation of uterine contractility.

Indexed as

Uterine ContractionAnimalsCalciumCalmodulin-Binding ProteinsExtracellular Signal-Regulated MAP KinasesFemaleFocal AdhesionsHumansMyometriumPhosphorylationPregnancyRatsRats, Sprague-DawleySignal TransductionUterusCalciumCalmodulin-Binding ProteinsExtracellular Signal-Regulated MAP Kinases

Identifiers

PMID19834610
PMCPMC2759504
OpenAlexW2105782941

What OpenQuestion holds

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LicenceCC BY
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.