ArticleNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2019
Dickkopf-3 in aberrant endothelial secretome triggers renal fibroblast activation and endothelial-mesenchymal transition.
Article in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- The role of urinary Dickkopf-3 in the prediction of acute kidney injury: a systematic review meta-analysis.International urology and nephrology · 2023Pooled it
- A review of the sirtuins family: pivotal regulators and emerging therapeutic targets in renal fibrosis.Renal failure · 2026Review
- Pericyte-myofibroblast transition: a novel mechanism in peritoneal fibrosis and the effect of Asiaticoside.Journal of advanced research · 2026Article
- Non-invasive assessment techniques for renal fibrosis: advances and perspectives.Renal failure · 2025Review
- Molecular mechanisms of endothelial-mesenchymal transition and its pathophysiological feature in cerebrovascular disease.Cell & bioscience · 2025Review
- Urinary Dickkopf-3 Reflects Disease Severity and Predicts Short-Term Kidney Function Decline in Renal Ciliopathies.Kidney international reports · 2025Article
- DKK3 promotes renal fibrosis by increasing MFF-mediated mitochondrial dysfunction in Wnt/β-catenin pathway-dependent manner.Renal failure · 2024Article
- Pathophysiology in Brain Arteriovenous Malformations: Focus on Endothelial Dysfunctions and Endothelial-to-Mesenchymal Transition.Biomedicines · 2024Review
- Urinary Dickkopf 3 Is Not an Independent Risk Factor in a Cohort of Kidney Transplant Recipients and Living Donors.International journal of molecular sciences · 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
- Fibroblasts and endothelial cells interplay drives hypertrophic scar formation: Insights from in vitro and in vivo models.Bioengineering & translational medicine · 2024Article
- Single-Cell RNA-Seq Reveals Coronary Heterogeneity and Identifies CD133Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Dormant tumors circumvent tumor-specific adaptive immunity by establishing a Treg-dominated niche via DKK3.JCI insight · 2023Article
- End binding-3 inhibitor activates regenerative program in age-related macular degeneration.Cell reports. Medicine · 2023Article
- Patterns of Dickkopf-3 Serum and Urine Levels at Different Stages of Chronic Kidney Disease.Journal of clinical medicine · 2023Article
- DKK3 expression is associated with immunosuppression and poor prognosis in glioblastoma, in contrast to lower-grade gliomas.BMC neurology · 2023Article
- Immuno-histochemical correlation of fibrosis-related markers with the desmoplastic reaction of the mesentery in small intestine neuroendocrine neoplasms.Journal of cancer research and clinical oncology · 2023Article
- Urinary Dickkopf-3 (DKK3) Is Associated with Greater eGFR Loss in Patients with Resistant Hypertension.Journal of clinical medicine · 2023Article
- High DKK3 expression related to immunosuppression was associated with poor prognosis in glioblastoma: machine learning approach.Cancer immunology, immunotherapy : CII · 2022Article
- Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Background: Our laboratory has previously demonstrated that Sirt1endo-/- mice show endothelial dysfunction and exaggerated renal fibrosis, whereas mice with silenced endothelial transforming growth factor beta (TGF-β) signaling are resistant to fibrogenic signals. Considering the fact that the only difference between these mutant mice is confined to the vascular endothelium, this indicates that secreted substances contribute to these contrasting responses. Methods: We performed an unbiased proteomic analysis of the secretome of renal microvascular endothelial cells (RMVECs) isolated from these two mutants. We cultured renal fibroblasts and RMVECs and used microfluidic devices for coculturing. Results: Dickkopf-3 (DKK3), a putative ligand of the Wnt/β-catenin pathway, was present exclusively in the fibrogenic secretome. In cultured fibroblasts, DKK3 potently induced myofibroblast activation. In addition, DKK3 antagonized effects of DKK1, a known inhibitor of the Wnt pathway, in conversion of fibroblasts to myofibroblasts. In RMVECs, DKK3 induced endothelial-mesenchymal transition and impaired their angiogenic competence. The inhibition of endothelial outgrowth, enhanced myofibroblast formation and endothelial-mesenchymal transition were confirmed in coculture. In reporter DKK3-eGFP × Col3.6-GFPcyan mice, DKK3 was marginally expressed under basal conditions. Adriamycin-induced nephropathy resulted in upregulation of DKK3 expression in tubular and, to a lesser degree, endothelial compartments. Sulindac sulfide was found to exhibit superior Wnt pathway-suppressive action and decreased DKK3 signals and the extent of renal fibrosis. Conclusions: In conclusion, this unbiased proteomic screen of the profibrogenic endothelial secretome revealed DKK3 acting as an agonist of the Wnt pathway, enhancing formation of myofibroblasts and endothelial-mesenchymal transition and impairing angiogenesis. A potent inhibitor of the Wnt pathway, sulindac sulfide, suppressed nephropathy-induced DKK3 expression and renal fibrosis.
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Registered trials
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.