ArticleThe Journal of cell biology2016
Plakophilin-2 loss promotes TGF-β1/p38 MAPK-dependent fibrotic gene expression in cardiomyocytes.
Article in The Journal of cell biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 118 citations in OpenAlex.
- Desmoplakin Mutations in Cardiac Fibroblasts Cause TGFβ1-Mediated Pathological Fibrogenesis in Desmoplakin Cardiomyopathy Via Beclin-1 Regulation.Circulation research · 2026Article
- Desmoplakin loss in alveolar epithelium drives Wnt/β-Catenin-mediated extracellular matrix remodeling and fibrotic signaling in vitro.Molecular biology reports · 2026Article
- TGF-β2 signaling promotes cardiac fibrosis in arrhythmogenic right ventricular cardiomyopathy mediated by DSC2 deficiency.Acta pharmacologica Sinica · 2026Article
- Epicardial Contributions to Fibro-Inflammatory Signaling in a Pkp2-Deficient Arrhythmogenic Cardiomyopathy Model.Circulation. Heart failure · 2026Article
- Proteomics analysis of empagliflozin in patients without diabetes or overt heart failure from empagliflozin and cardiac remodeling in people without diabetes CardioLink-7 randomized clinical trial.Cardiovascular endocrinology & metabolism · 2026Article
- RhoGEF Ect2 supports RhoA activity at cell-cell junctions through desmoplakin.Life science alliance · 2026Article
- Disease models and AAV therapies ofMolecular therapy. Advances · 2026Review
- Maintenance of Energy Metabolism Is an Integral Part of Plakophilin-2 and Desmosome Functions.JACC. Basic to translational science · 2025Article
- Gene Therapy TargetingMedComm · 2025Article
- Cardiac dysfunction and altered gene expression in acid ceramidase-deficient mice.American journal of physiology. Heart and circulatory physiology · 2025Article
- The desmosomal cadherin Desmoglein-2 controls extracellular matrix expression and remodeling via NF-κB signaling in keratinocytes.Frontiers in cell and developmental biology · 2025Article
- Novel ocular observations in a child with Joubert syndrome type 6 due to pathogenic variant inAmerican journal of ophthalmology case reports · 2024Article
- Hyperactivation of ATF4/TGF-β1 signaling contributes to the progressive cardiac fibrosis in Arrhythmogenic cardiomyopathy caused by DSG2 Variant.BMC medicine · 2024Article
- Animal Models and Molecular Pathogenesis of Arrhythmogenic Cardiomyopathy Associated with Pathogenic Variants in Intercalated Disc Genes.International journal of molecular sciences · 2024Review
- AAV9:PKP2 improves heart function and survival in a Pkp2-deficient mouse model of arrhythmogenic right ventricular cardiomyopathy.Communications medicine · 2024Article
- Role of desmoplakin in supporting neuronal activity, neurogenic processes, and emotional-related behaviors in the dentate gyrus.Frontiers in neuroscience · 2024Article
- Overexpression of Plakophilin2 Mitigates Capillary Leak Syndrome in Severe Acute Pancreatitis by Activating the p38/MAPK Signaling Pathway.Journal of inflammation research · 2024Article
- Understanding Arrhythmogenic Cardiomyopathy: Advances through the Use of Human Pluripotent Stem Cell Models.Genes · 2023Review
- Review
- Impaired Plakophilin-2 in obesity breaks cell cycle dynamics to breed adipocyte senescence.Nature communications · 2023Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Members of the desmosome protein family are integral components of the cardiac area composita, a mixed junctional complex responsible for electromechanical coupling between cardiomyocytes. In this study, we provide evidence that loss of the desmosomal armadillo protein Plakophilin-2 (PKP2) in cardiomyocytes elevates transforming growth factor β1 (TGF-β1) and p38 mitogen-activated protein kinase (MAPK) signaling, which together coordinate a transcriptional program that results in increased expression of profibrotic genes. Importantly, we demonstrate that expression of Desmoplakin (DP) is lost upon PKP2 knockdown and that restoration of DP expression rescues the activation of this TGF-β1/p38 MAPK transcriptional cascade. Tissues from PKP2 heterozygous and DP conditional knockout mouse models also exhibit elevated TGF-β1/p38 MAPK signaling and induction of fibrotic gene expression in vivo. These data therefore identify PKP2 and DP as central players in coordination of desmosome-dependent TGF-β1/p38 MAPK signaling in cardiomyocytes, pathways known to play a role in different types of cardiac disease, such as arrhythmogenic or hypertrophic cardiomyopathy.
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Registered trials
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