ArticleKidney international2016
Experimental inhibition of porcupine-mediated Wnt O-acylation attenuates kidney fibrosis.
Article in Kidney international, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 64 citations in OpenAlex.
- Maternal Obesity Induces DNA Methylation Changes in the Kidneys and Blood of Rodent Offspring at Adulthood.Nutrients · 2026Article
- Shared mechanisms of organ fibrosis.JCI insight · 2026Review
- Understanding the Mechanisms Driving Fibrosis Following Cochlear Implantation-Lessons from Other Tissues.Cells · 2025Review
- Epithelial Cell Dysfunction in Pulmonary Fibrosis: Mechanisms, Interactions, and Emerging Therapeutic Targets.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Personalized Antifibrotic Therapy in CKD Progression.Journal of personalized medicine · 2024Review
- Noncanonical WNT5A controls the activation of latent TGF-β to drive fibroblast activation and tissue fibrosis.The Journal of clinical investigation · 2024Article
- Characterising the Effect of Wnt/β-Catenin Signalling on Melanocyte Development and Patterning: Insights from Zebrafish (International journal of molecular sciences · 2023Article
- The role of Evi/Wntless in exporting Wnt proteins.Development (Cambridge, England) · 2023Review
- Small-molecule Wnt inhibitors are a potential novel therapy for intestinal fibrosis in Crohns disease.Clinical science (London, England : 1979) · 2022Article
- Targeting ligand-dependent wnt pathway dysregulation in gastrointestinal cancers through porcupine inhibition.Pharmacology & therapeutics · 2022Review
- The Wnt Pathway Inhibitor RXC004 Blocks Tumor Growth and Reverses Immune Evasion in Wnt Ligand-dependent Cancer Models.Cancer research communications · 2022Article
- Deletion of STAT3 from Foxd1 cell population protects mice from kidney fibrosis by inhibiting pericytes trans-differentiation and migration.Cell reports · 2022Article
- Wnt-C59 inhibits proinflammatory cytokine expression by reducing the interaction between β-catenin and NF-κB in LPS-stimulated epithelial and macrophage cells.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2021Article
- WNT-β-catenin signalling - a versatile player in kidney injury and repair.Nature reviews. Nephrology · 2021Review
- Role of SIK1 in the transition of acute kidney injury into chronic kidney disease.Journal of translational medicine · 2021Article
- Pharmacologically Targeting the WNT/β-Catenin Signaling Cascade: Avoiding the Sword of Damocles.Handbook of experimental pharmacology · 2021Article
- Pten deletion in Dmp1-expressing cells does not rescue the osteopenic effects of Wnt/β-catenin suppression.Journal of cellular physiology · 2020Article
- Article
- The varying roles of macrophages in kidney injury and repair.Current opinion in nephrology and hypertension · 2020Review
- Wnt/β-Catenin in Acute Kidney Injury and Progression to Chronic Kidney Disease.Seminars in nephrology · 2020Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Activated Wnt signaling is critical in the pathogenesis of renal fibrosis, a final common pathway for most forms of chronic kidney disease. Therapeutic intervention by inhibition of individual Wnts or downstream Wnt/β-catenin signaling has been proposed, but these approaches do not interrupt the functions of all Wnts nor block non-canonical Wnt signaling pathways. Alternatively, an orally bioavailable small molecule, Wnt-C59, blocks the catalytic activity of the Wnt-acyl transferase porcupine, and thereby prevents secretion of all Wnt isoforms. We found that inhibiting porcupine dramatically attenuates kidney fibrosis in the murine unilateral ureteral obstruction model. Wnt-C59 treatment similarly blunts collagen mRNA expression in the obstructed kidney. Consistent with its actions to broadly arrest Wnt signaling, porcupine inhibition reduces expression of Wnt target genes and bolsters nuclear exclusion of β-catenin in the kidney following ureteral obstruction. Importantly, prevention of Wnt secretion by Wnt-C59 blunts expression of inflammatory cytokines in the obstructed kidney that otherwise provoke a positive feedback loop of Wnt expression in collagen-producing fibroblasts and epithelial cells. Thus, therapeutic targeting of porcupine abrogates kidney fibrosis not only by overcoming the redundancy of individual Wnt isoforms but also by preventing upstream cytokine-induced Wnt generation. These findings reveal a novel therapeutic maneuver to protect the kidney from fibrosis by interrupting a pathogenic crosstalk loop between locally generated inflammatory cytokines and the Wnt/β-catenin signaling pathway.
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Registered trials
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