Evidence map›Paper›PMID 31284728›Full record

ArticleCirculation2019

Widespread Translational Control of Fibrosis in the Human Heart by RNA-Binding Proteins.

Sonia Chothani, Sebastian Schäfer, Eleonora Adami, Sivakumar Viswanathan, Anissa A Widjaja, Sarah R Langley, Jessie Tan, Mao Wang, Nicholas M Quaife, Chee Jian Pua and 16 more

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

Article in Circulation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed
6.8field-weighted citation impact, top 2% 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

83 citing papers in PubMed, 126 citations in OpenAlex.

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  16. From Epithelium to Therapy: Transitional Cells in Lung Fibrosis.American journal of respiratory cell and molecular biology · 2025
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23 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors at 5 institutions in 4 countries.

Sonia ChothaniProgram in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School, Singapore (S.C., S.S., E.A., S.V., A.W., S.L., M.W., G.D., S.G.S., B.L.G., S.L., E.Y.C., E.C., J.D., S.A.C., O.J.L.R.).
Sebastian SchäferProgram in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School, Singapore (S.C., S.S., E.A., S.V., A.W., S.L., M.W., G.D., S.G.S., B.L.G., S.L., E.Y.C., E.C., J.D., S.A.C., O.J.L.R.).
Eleonora AdamiProgram in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School, Singapore (S.C., S.S., E.A., S.V., A.W., S.L., M.W., G.D., S.G.S., B.L.G., S.L., E.Y.C., E.C., J.D., S.A.C., O.J.L.R.).
Sivakumar ViswanathanProgram in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School, Singapore (S.C., S.S., E.A., S.V., A.W., S.L., M.W., G.D., S.G.S., B.L.G., S.L., E.Y.C., E.C., J.D., S.A.C., O.J.L.R.).
Anissa A WidjajaProgram in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School, Singapore (S.C., S.S., E.A., S.V., A.W., S.L., M.W., G.D., S.G.S., B.L.G., S.L., E.Y.C., E.C., J.D., S.A.C., O.J.L.R.).
Sarah R LangleyProgram in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School, Singapore (S.C., S.S., E.A., S.V., A.W., S.L., M.W., G.D., S.G.S., B.L.G., S.L., E.Y.C., E.C., J.D., S.A.C., O.J.L.R.).
Jessie TanNational Heart Centre Singapore, Singapore (S.S., S.L., J.T., C.J.P., S.A.C.).
Mao WangProgram in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School, Singapore (S.C., S.S., E.A., S.V., A.W., S.L., M.W., G.D., S.G.S., B.L.G., S.L., E.Y.C., E.C., J.D., S.A.C., O.J.L.R.).
Nicholas M QuaifeNational Heart and Lung Institute, Imperial College London, United Kingdom (N.M.Q., L.E.F., P.J.R.B., S.A.C.).
Chee Jian PuaNational Heart Centre Singapore, Singapore (S.S., S.L., J.T., C.J.P., S.A.C.).
Giuseppe D'AgostinoProgram in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School, Singapore (S.C., S.S., E.A., S.V., A.W., S.L., M.W., G.D., S.G.S., B.L.G., S.L., E.Y.C., E.C., J.D., S.A.C., O.J.L.R.).
Shamini Guna ShekeranProgram in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School, Singapore (S.C., S.S., E.A., S.V., A.W., S.L., M.W., G.D., S.G.S., B.L.G., S.L., E.Y.C., E.C., J.D., S.A.C., O.J.L.R.).
Benjamin L GeorgeProgram in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School, Singapore (S.C., S.S., E.A., S.V., A.W., S.L., M.W., G.D., S.G.S., B.L.G., S.L., E.Y.C., E.C., J.D., S.A.C., O.J.L.R.).
Stella LimProgram in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School, Singapore (S.C., S.S., E.A., S.V., A.W., S.L., M.W., G.D., S.G.S., B.L.G., S.L., E.Y.C., E.C., J.D., S.A.C., O.J.L.R.).
Elaine Yiqun CaoProgram in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School, Singapore (S.C., S.S., E.A., S.V., A.W., S.L., M.W., G.D., S.G.S., B.L.G., S.L., E.Y.C., E.C., J.D., S.A.C., O.J.L.R.).
Sebastiaan van HeeschCardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (E.A., S.v.H., F.W., S.B., G.P., N.H.).
Franziska WitteCardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (E.A., S.v.H., F.W., S.B., G.P., N.H.).
Leanne E FelkinNational Heart and Lung Institute, Imperial College London, United Kingdom (N.M.Q., L.E.F., P.J.R.B., S.A.C.).
Eleni G ChristodoulouProgram in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School, Singapore (S.C., S.S., E.A., S.V., A.W., S.L., M.W., G.D., S.G.S., B.L.G., S.L., E.Y.C., E.C., J.D., S.A.C., O.J.L.R.).
Jinrui DongProgram in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School, Singapore (S.C., S.S., E.A., S.V., A.W., S.L., M.W., G.D., S.G.S., B.L.G., S.L., E.Y.C., E.C., J.D., S.A.C., O.J.L.R.).
Susanne BlachutCardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (E.A., S.v.H., F.W., S.B., G.P., N.H.).
Giannino PatoneCardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (E.A., S.v.H., F.W., S.B., G.P., N.H.).
Paul J R BartonNational Heart and Lung Institute, Imperial College London, United Kingdom (N.M.Q., L.E.F., P.J.R.B., S.A.C.).
Norbert HubnerCardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany (E.A., S.v.H., F.W., S.B., G.P., N.H.).
Stuart A CookProgram in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School, Singapore (S.C., S.S., E.A., S.V., A.W., S.L., M.W., G.D., S.G.S., B.L.G., S.L., E.Y.C., E.C., J.D., S.A.C., O.J.L.R.).
Owen J L RackhamProgram in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School, Singapore (S.C., S.S., E.A., S.V., A.W., S.L., M.W., G.D., S.G.S., B.L.G., S.L., E.Y.C., E.C., J.D., S.A.C., O.J.L.R.).
S.P.E.C.I.E.S. · USHelmholtz Association of German Research Centres · DENational Heart Centre Singapore · SGHammersmith Hospital · GBLung Institute · US

Funding

Medical Research Council MC_U120085815
6 · The paper itself

Abstract

backgroundFibrosis is a common pathology in many cardiac disorders and is driven by the activation of resident fibroblasts. The global posttranscriptional mechanisms underlying fibroblast-to-myofibroblast conversion in the heart have not been explored.

methodsGenome-wide changes of RNA transcription and translation during human cardiac fibroblast activation were monitored with RNA sequencing and ribosome profiling. We then used RNA-binding protein-based analyses to identify translational regulators of fibrogenic genes. The integration with cardiac ribosome occupancy levels of 30 dilated cardiomyopathy patients demonstrates that these posttranscriptional mechanisms are also active in the diseased fibrotic human heart.

resultsWe generated nucleotide-resolution translatome data during the transforming growth factor β1-driven cellular transition of human cardiac fibroblasts to myofibroblasts. This identified dynamic changes of RNA transcription and translation at several time points during the fibrotic response, revealing transient and early-responder genes. Remarkably, about one-third of all changes in gene expression in activated fibroblasts are subject to translational regulation, and dynamic variation in ribosome occupancy affects protein abundance independent of RNA levels. Targets of RNA-binding proteins were strongly enriched in posttranscriptionally regulated genes, suggesting genes such as MBNL2 can act as translational activators or repressors. Ribosome occupancy in the hearts of patients with dilated cardiomyopathy suggested the same posttranscriptional regulatory network was underlying cardiac fibrosis. Key network hubs include RNA-binding proteins such as Pumilio RNA binding family member 2 (PUM2) and Quaking (QKI) that work in concert to regulate the translation of target transcripts in human diseased hearts. Furthermore, silencing of both PUM2 and QKI inhibits the transition of fibroblasts toward profibrotic myofibroblasts in response to transforming growth factor β1.

conclusionsWe reveal widespread translational effects of transforming growth factor β1 and define novel posttranscriptional regulatory networks that control the fibroblast-to-myofibroblast transition. These networks are active in human heart disease, and silencing of hub genes limits fibroblast activation. Our findings show the central importance of translational control in fibrosis and highlight novel pathogenic mechanisms in heart failure.

Indexed as

Cells, CulturedFibroblastsFibrosisGene Expression ProfilingHeart DiseasesHumansMyocytes, CardiacProtein BiosynthesisRNA-Binding ProteinsSequence Analysis, RNATransforming Growth Factor beta1RNA-Binding ProteinsTGFB1 protein, humanTransforming Growth Factor beta1dilated cardiomyopathyfibrosisribosome profilingRNA-binding proteinsTGF-beta1

Identifiers

PMID31284728
PMCPMC6749977
OpenAlexW2958340383

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LicenceCC BY
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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.