Evidence map›Paper›PMID 42615127›Full record

ArticleCirculation research2026

Desmoplakin Mutations in Cardiac Fibroblasts Cause TGFβ1-Mediated Pathological Fibrogenesis in Desmoplakin Cardiomyopathy Via Beclin-1 Regulation.

Chuanyu Wei, Weinian Shou, Shing-Fai Chan, Ardan M Saguner, Corinna Brunckhorst, Firat Duru, Joseph E Marine, Cynthia A James, Hugh Calkins, Daniel P Judge and 1 more

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Article in Circulation research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

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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

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No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Chuanyu WeiKrannert Cardiovascular Research Center, Department of Medicine (C.W., S-F.C., H-S.V.C.), Indiana University School of Medicine, Indianapolis.
Weinian ShouRiley Heart Research Center, Herman B Wells Center for Pediatric Research, Department of Pediatrics (W.S.), Indiana University School of Medicine, Indianapolis.ORCID 0000-0001-5538-9605
Shing-Fai ChanKrannert Cardiovascular Research Center, Department of Medicine (C.W., S-F.C., H-S.V.C.), Indiana University School of Medicine, Indianapolis.ORCID 0000-0001-6988-4631
Ardan M SagunerDepartment of Cardiology, University Heart Center, University Hospital Zurich (A.M.S., C.B., F.D.).ORCID 0000-0003-1896-0803
Corinna BrunckhorstDepartment of Cardiology, University Heart Center, University Hospital Zurich (A.M.S., C.B., F.D.).
Firat DuruDepartment of Cardiology, University Heart Center, University Hospital Zurich (A.M.S., C.B., F.D.).ORCID 0000-0002-4748-0158
Joseph E MarineDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD (J.E.M., C.A.J., H. C.).ORCID 0000-0001-5035-5342
Cynthia A JamesDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD (J.E.M., C.A.J., H. C.).ORCID 0000-0001-8040-4600
Hugh CalkinsDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD (J.E.M., C.A.J., H. C.).ORCID 0000-0002-9262-9433
Daniel P JudgeDivision of Cardiology, Medical University of South Carolina, Charleston (D.P.J.).ORCID 0000-0002-3407-0248
Huei-Sheng Vincent ChenKrannert Cardiovascular Research Center, Department of Medicine (C.W., S-F.C., H-S.V.C.), Indiana University School of Medicine, Indianapolis.ORCID 0000-0002-5235-2505

Funding

Maturation of Normal and Disease-specific Human Stem Cell-derived CardiomyocytesR01HL105194 · NHLBI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI CHEN, HUEI-SHENG VINCENT · 2010 to 2014
$2.4M
Non-junctional roles of desmosome proteins in the pathogenesis of arrhythmogenic cardiomyopathyR56HL161741 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI CHEN, HUEI-SHENG VINCENT · 2022 to 2022
$502k
NHLBI NIH HHS R01 HL105194NHLBI NIH HHS R56 HL161741
6 · The paper itself

Abstract

backgroundPathological fibrosis is a major finding in cardiovascular diseases and can result in arrhythmia and heart failure. Desmosome gene mutations can lead to arrhythmogenic cardiomyopathy. Among arrhythmogenic cardiomyopathies, pathogenic

methodsMesenchymal stromal cells (MSCs) are resident fibroblast-like cells that are responsible for fibrogenesis in most organs, including the heart. We first used RNA-seq genome-wide analyses to generate cardiac fibroblast-like, induced pluripotent stem cell-derived MSCs from normal donors and patients with arrhythmogenic cardiomyopathy and

resultsTGFβ1 induced excessive accumulation of VIM (vimentin)/fibrillar collagens and over-activated fibrotic genes in

conclusionsOur data reveal that DSP deficiency in MSCs/fibroblasts leads to exaggerated fibrogenesis in DSP-cardiomyopathy by decreasing BECN1 availability for autophagy and CAV1-endocytosis. Overexpression of VIM binding domains of DSP could be a new strategy to treat pathological fibrosis.

Indexed as

Beclin-1CardiomyopathiesDesmoplakinsFibroblastsMutationMyocardiumTransforming Growth Factor beta1AnimalsAutophagyCaveolin 1Cells, CulturedFibrosisHumansMesenchymal Stem CellsMiceMice, Inbred C57BLBeclin-1Caveolin 1DesmoplakinsDSP protein, humanDsp protein, mouseTGFB1 protein, humanTransforming Growth Factor beta1autophagycaveolin 1collagenendocytosisfibrosisp38 mitogen-activated protein kinasesvimentin

Identifiers

PMID42615127
PMCPMC13574352

What OpenQuestion holds

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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.