ArticleJournal of the American Society of Nephrology : JASN2010
Dickkopf-1 promotes hyperglycemia-induced accumulation of mesangial matrix and renal dysfunction.
Article in Journal of the American Society of Nephrology : JASN, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 96 citations in OpenAlex.
- Alterations in bone turnover markers in patients with noncardio-embolic ischemic stroke.PloS one · 2018Trial
- Emerging therapeutic pipelines on kidney fibrosis: challenges in translational research.Journal of translational medicine · 2026Review
- Review
- Usefulness of DKK1 in Estimating Vasculitis Activity and End-Stage Kidney Disease in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Patients.Yonsei medical journal · 2026Article
- Tetramethylpyrazine alleviates acute kidney injury by activating the Wnt/β-catenin pathway independent of DKK1.Experimental and therapeutic medicine · 2025Article
- Plasma Dickkopf-1 Levels Are Associated with Chronic Kidney Disease.Metabolites · 2025Article
- Bone-derived factors mediate crosstalk between skeletal and extra-skeletal organs.Bone research · 2025Review
- The Dual Role and Therapeutic Implications of the Wnt/β-Catenin Pathway in Diabetic Kidney Disease.International journal of general medicine · 2025Review
- Podocyte-targeted therapies - progress and future directions.Nature reviews. Nephrology · 2024Review
- Synergistic modulation of endoplasmic reticulum stress pathway, oxidative DNA damage and apoptosis by β-amyrin and metformin in mitigating hyperglycemia-induced renal damage using adult zebrafish model.BMC pharmacology & toxicology · 2024Article
- Dickkopf-1 (DKK1) blockade mitigates osteogenesis imperfecta (OI) related bone disease.Molecular medicine (Cambridge, Mass.) · 2024Article
- To Explore the Putative Molecular Targets of Diabetic Nephropathy and their Inhibition Utilizing Potential Phytocompounds.Current medicinal chemistry · 2024Review
- Ascorbate protects human kidney organoids from damage induced by cell-free hemoglobin.Disease models & mechanisms · 2023Article
- Pathomechanisms of Diabetic Kidney Disease.Journal of clinical medicine · 2023Review
- Insight into the Molecular Mechanism of Diabetic Kidney Disease and the Role of Metformin in Its Pathogenesis.International journal of molecular sciences · 2023Review
- Dickkopf-1 Acts as a Profibrotic Mediator in Progressive Chronic Kidney Disease.International journal of molecular sciences · 2023Article
- Sestrin2 attenuates renal damage by regulating Hippo pathway in diabetic nephropathy.Cell and tissue research · 2022Article
- The Histone Demethylase Inhibitor GSK-J4 Is a Therapeutic Target for the Kidney Fibrosis of Diabetic Kidney Disease via DKK1 Modulation.International journal of molecular sciences · 2022Article
- Signaling pathways of chronic kidney diseases, implications for therapeutics.Signal transduction and targeted therapy · 2022Review
- Knockout of KLF10 Ameliorated Diabetic Renal Fibrosis via Downregulation of DKK-1.Molecules (Basel, Switzerland) · 2022Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
Abstract
Wnt/beta-catenin signaling mediates renal fibrosis in several model systems including diabetic nephropathy. Dickkopf-1 (DKK-1) is an endogenous inhibitor of Wnt/beta-catenin signaling, but whether DKK-1 modulates diabetic nephropathy is unknown. Here, we studied whether DKK-1 participates in high glucose (HG)-induced expression of profibrotic factors and renal damage. In vitro, HG increased expression of DKK1, receptor Kremen-2, TGF-beta1, and fibronectin in mesangial cells. Loss and gain of DKK1 function modulated HG-mediated c-Jun, TGF-beta1, and fibronectin expression. DKK1 mediated HG-induced phosphorylation of Ser45-beta-catenin and reduction of nuclear beta-catenin levels, but not phosphorylation of ERK kinase. Wnt3a protein and the beta-catenin (Delta45) mutation increased nuclear beta-catenin but abrogated HG-induced DKK1 and fibronectin expression. Exogenous DKK1 antisense oligonucleotide attenuated the increase in both serum DKK1 and urinary protein excretion in streptozotocin-induced diabetic rats. Knocking down DKK1 inhibited mesangial expression of TGF-beta1 and fibronectin and reduced both the glomerular volume and deposition of mesangial matrix in diabetic kidneys. Taken together, DKK1 mediates HG-induced destabilization of beta-catenin and matrix accumulation in mesangial cells. Knocking down DKK1 prevents diabetes-induced renal dysfunction and microstructure deterioration, suggesting that inhibition of DKK1offers therapeutic potential for diabetic nephropathy.
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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 Socratic graph.