Evidence map›Paper›PMID 32883176›Full record

ArticleCirculation research2020

Infarct Collagen Topography Regulates Fibroblast Fate via p38-Yes-Associated Protein Transcriptional Enhanced Associate Domain Signals.

Darrian Bugg, Ross Bretherton, Peter Kim, Emily Olszewski, Abigail Nagle, Austin E Schumacher, Nick Chu, Jagadambika Gunaje, Cole A DeForest, Kelly Stevens and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Circulation research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 1 pooled it
4.5field-weighted citation impact, top 4% 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

51 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.

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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

12 authors at 4 institutions in 2 countries.

Darrian Bugg *Pathology (D.B., J.G., K.S., J.D.), University of Washington, Seattle.
Ross Bretherton *Bioengineering (R.B., P.K., E.O., A.N., N.C., C.A.D., K.S., J.D.), University of Washington, Seattle.
Peter Kim *Bioengineering (R.B., P.K., E.O., A.N., N.C., C.A.D., K.S., J.D.), University of Washington, Seattle.
Emily OlszewskiBioengineering (R.B., P.K., E.O., A.N., N.C., C.A.D., K.S., J.D.), University of Washington, Seattle.
Abigail NagleBioengineering (R.B., P.K., E.O., A.N., N.C., C.A.D., K.S., J.D.), University of Washington, Seattle.
Austin E SchumacherBiostatistics (A.E.S.), University of Washington, Seattle.
Nick ChuBioengineering (R.B., P.K., E.O., A.N., N.C., C.A.D., K.S., J.D.), University of Washington, Seattle.
Jagadambika GunajePathology (D.B., J.G., K.S., J.D.), University of Washington, Seattle.
Cole A DeForestBioengineering (R.B., P.K., E.O., A.N., N.C., C.A.D., K.S., J.D.), University of Washington, Seattle.
Kelly StevensBioengineering (R.B., P.K., E.O., A.N., N.C., C.A.D., K.S., J.D.), University of Washington, Seattle.
Deok-Ho KimBiomedical Engineering, Johns Hopkins University, Baltimore, MD (D.-H.K.).
Jennifer DavisCenter for Cardiovascular Biology (D.B., R.B., E.O., A.N., J.G., K.S., J.D.), University of Washington, Seattle.
University of Washington · USBioengineering Center · RUCalifornia Institute for Regenerative Medicine · USJohns Hopkins University · US

Funding

Integrating Transcriptome Reprogramming Into Cardiac Plasticity Regulatory MechanismsR01HL141187 · NHLBI · UNIVERSITY OF WASHINGTON · PI Jennifer Michelle Davis · 2018 to 2026
$4.0M
Uncovering The Mechanogenomic Basis For Cardiac PlasticityR01HL142624 · NHLBI · UNIVERSITY OF WASHINGTON · PI Jennifer Michelle Davis · 2018 to 2026
$3.8M
Thermogenetic activation of engineered tissue for cardiac repairDP2HL137188 · NHLBI · UNIVERSITY OF WASHINGTON · PI STEVENS, KELLY R · 2016 to 2016
$2.6M
DISEASE MODELING AND PHENOTYPIC DRUG SCREENING FOR DYSTROPHIC CARDIOMYOPATHYR01HL146436 · NHLBI · UNIVERSITY OF WASHINGTON · PI KIM, DEOK-HO · 2019 to 2022
$2.2M
A NANOPATTERNED MEA-BASED FUNCTIONAL PHENOTYPING ASSAY FOR DRUG-INDUCED CARDIOTOXICITY SCREENINGR01HL135143 · NHLBI · UNIVERSITY OF WASHINGTON · PI KIM, DEOK-HO · 2017 to 2021
$1.9M
A HUMAN IPSC-BASED 3D MICROPHYSIOLOGICAL SYSTEM FOR MODELING CARDIAC DYSFUNCTION IN MICROGRAVITYUG3EB028094 · NIBIB · UNIVERSITY OF WASHINGTON · PI KIM, DEOK-HO · 2018 to 2019
$1.5M
Elucidating the role of cardiac myofibroblasts on matrix and vasculature remodelingF31HL151017 · NHLBI · UNIVERSITY OF WASHINGTON · PI OLSZEWSKI, EMILY · 2020 to 2022
$85k
NHLBI NIH HHS DP2 HL137188NHLBI NIH HHS F31 HL151017NHLBI NIH HHS R01 HL135143NHLBI NIH HHS R01 HL141187NHLBI NIH HHS R01 HL142624NHLBI NIH HHS R01 HL146436NIBIB NIH HHS UG3 EB028094
6 · The paper itself

Abstract

rationaleMyocardial infarction causes spatial variation in collagen organization and phenotypic diversity in fibroblasts, which regulate the heart's ECM (extracellular matrix). The relationship between collagen structure and fibroblast phenotype is poorly understood but could provide insights regarding the mechanistic basis for myofibroblast heterogeneity in the injured heart.

objectiveTo investigate the role of collagen organization in cardiac fibroblast fate determination. METHODS AND

resultsBiomimetic topographies were nanofabricated to recapitulate differential collagen organization in the infarcted mouse heart. Here, adult cardiac fibroblasts were freshly isolated and cultured on ECM topographical mimetics for 72 hours. Aligned mimetics caused cardiac fibroblasts to elongate while randomly organized topographies induced circular morphology similar to the disparate myofibroblast morphologies measured in vivo. Alignment cues also induced myofibroblast differentiation, as >60% of fibroblasts formed αSMA (α-smooth muscle actin) stress fibers and expressed myofibroblast-specific ECM genes like Postn (periostin). By contrast, random organization caused 38% of cardiac fibroblasts to express αSMA albeit with downregulated myofibroblast-specific ECM genes. Coupling topographical cues with the profibrotic agonist, TGFβ (transforming growth factor beta), additively upregulated myofibroblast-specific ECM genes independent of topography, but only fibroblasts on flat and randomly oriented mimetics had increased percentages of fibroblasts with αSMA stress fibers. Increased tension sensation at focal adhesions induced myofibroblast differentiation on aligned mimetics. These signals were transduced by p38-YAP (yes-associated protein)-TEAD (transcriptional enhanced associate domain) interactions, in which both p38 and YAP-TEAD (yes-associated protein transcriptional enhanced associate domain) binding were required for myofibroblast differentiation. By contrast, randomly oriented mimetics did not change focal adhesion tension sensation or enrich for p38-YAP-TEAD interactions, which explains the topography-dependent diversity in fibroblast phenotypes observed here.

conclusionsSpatial variations in collagen organization regulate cardiac fibroblast phenotype through mechanical activation of p38-YAP-TEAD signaling, which likely contribute to myofibroblast heterogeneity in the infarcted myocardium.

Indexed as

Cell DifferentiationSignal TransductionActinsAdaptor Proteins, Signal TransducingAnimalsCell Adhesion MoleculesCells, CulturedCollagenDNA-Binding ProteinsMiceMice, Inbred C57BLMyocardial InfarctionMyofibroblastsp38 Mitogen-Activated Protein KinasesStress FibersTEA Domain Transcription FactorsActa1 protein, mouseActinsAdaptor Proteins, Signal TransducingCell Adhesion MoleculesCollagenDNA-Binding Proteinsp38 Mitogen-Activated Protein KinasesPostn protein, mouseTead1 protein, mouseTEA Domain Transcription FactorsTranscription FactorsTransforming Growth Factor betaYap1 protein, mouseYAP-Signaling Proteinsextracellular matrixfibroblastsfibrosismyocardial infarctionnanotechnology

Identifiers

PMID32883176
PMCPMC7581544
OpenAlexW3083428666

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.