ArticleLaboratory investigation; a journal of technical methods and pathology2016
Dkk3 prevents familial dilated cardiomyopathy development through Wnt pathway.
Article in Laboratory investigation; a journal of technical methods and pathology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 56 citations in OpenAlex.
- Wnt-associated DKK3 in keratinocytes mediates radiation-induced hyperplasia, dermatitis and skin fibrosis.Signal transduction and targeted therapy · 2026Article
- Histone deacetylase 4: A therapeutic target for cardiovascular diseases (Review).International journal of molecular medicine · 2025Review
- Mitochondria associated membranes in dilated cardiomyopathy: connecting pathogenesis and cellular dysfunction.Frontiers in cardiovascular medicine · 2025Review
- Urinary Dickkopf-3 as a Potential Marker for Estimated Glomerular Filtration Rate Decline in Patients With Heart Failure.Journal of the American Heart Association · 2024Article
- The ChickenGenes · 2024Article
- Clinical-transcriptional prioritization of the circulating proteome in human heart failure.Cell reports. Medicine · 2024Article
- DKK3 promotes oxidative stress injury and fibrosis in HK-2 cells by activating NOX4 via β-catenin/TCF4 signaling.Molecular and cellular biochemistry · 2024Article
- Cas13b-mediated RNA targeted therapy alleviates genetic dilated cardiomyopathy in mice.Cell & bioscience · 2024Article
- Predictive value of glycoprotein DKK3 for early neurological deterioration after ischemic stroke.Clinics (Sao Paulo, Brazil) · 2024Article
- NRF1 knockdown alleviates lipopolysaccharide-induced pulmonary inflammatory injury by upregulating DKK3 and inhibiting the GSK-3β/β-catenin pathway.Clinical and experimental immunology · 2023Article
- Cardiac-specific Trim44 knockout in rat attenuates isoproterenol-induced cardiac remodeling via inhibition of AKT/mTOR pathway.Disease models & mechanisms · 2023Article
- Bioinformatics Analysis of Common Differential Genes of Viral Myocarditis and Dilated Cardiomyopathy: Screening for Potential Pharmacological Compounds.Journal of cardiovascular development and disease · 2022Article
- DKK3 ameliorates neuropathic pain via inhibiting ASK-1/JNK/p-38-mediated microglia polarization and neuroinflammation.Journal of neuroinflammation · 2022Article
- Review
- Deciphering Cell-Type-Specific Gene Expression Signatures of Cardiac Diseases Through Reconstruction of Bulk Transcriptomes.Frontiers in cell and developmental biology · 2022Article
- The emerging plasma biomarker Dickkopf-3 (DKK3) and its association with renal and cardiovascular disease in the general population.Scientific reports · 2021Article
- SARS-CoV-2 infection aggravates chronic comorbidities of cardiovascular diseases and diabetes in mice.Animal models and experimental medicine · 2021Article
- Article
- A combined bioinformatics, experimental and clinical approach to identify novel cardiac-specific heart failure biomarkers: is Dickkopf-3 (DKK3) a possible candidate?European journal of heart failure · 2020Article
- Transcriptome analysis of genes related to gonad differentiation and development in Muscovy ducks.BMC genomics · 2020Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To date, the role of Dickkopf 3 (Dkk3) on the pathogenesis of familial dilated cardiomyopathy (FDCM), and whether and how Dkk3 interferes with Wnt signaling in heart tissues remains unknown. Here, we demonstrate that strong Dkk3 expression was markedly downregulated in adult hearts from WT mice, and Dkk3 expression was upregulated suddenly in hearts from DCM mouse models. Using Dkk3 transgenic and knockout mice, as well as cTnT(R141W) transgenic mice, which manifests progressive chamber dilation and contractile dysfunction and has pathologic phenotypes similar to human DCM patients, we determined that transgenic expression of Dkk3 increased survival rate, improved cardiac morphology breakage and dysfunction, and ameliorated cardiac pathological changes in the cTnT(R141W) mice. In contrast, Dkk3 knockout reduced the survival rate and aggravated the pathological phenotypes of the cTnT(R141W) mice. The protective effects of Dkk3 appeared clearly at 3 months of age, peaked at 6 months of age, and decreased at 10 months of age in the cTnT(R141W) mice. Furthermore, we determined that Dkk3 upregulated Dvl1 (Dishevelled 1) and key proteins of the canonical Wnt pathway (cytoplasmic and nuclear β-catenin, c-Myc, and Axin2) and downregulated key proteins of the noncanonical Wnt pathway (c-Jun N-terminal kinase (JNK), Ca(2+)/calmodulin-dependent protein kinase II (CAMKII), and histone deacetylase 4 (HDAC4)). In contrast, Dkk3 knockout reversed these changes in the cTnT(R141W) mice. In summary, Dkk3 could prevent FDCM development in mice, especially in the compensatory stage, and probably through activation of the canonical and inhibition of the noncanonical Wnt pathway, which suggested that Dkk3 could serve as a therapeutic target for the treatment of cardiomyopathy and heart failure.
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