ArticleJournal of the American Society of Nephrology : JASN2015
Multiple genes of the renin-angiotensin system are novel targets of Wnt/β-catenin signaling.
Article in Journal of the American Society of Nephrology : JASN, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers, 1 of them a synthesis that pooled it.
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Who cites it
156 citing papers in PubMed, 1 synthesis or guideline pooled it, 230 citations in OpenAlex.
- Atlas of tissue renin-angiotensin-aldosterone system in human: A transcriptomic meta-analysis.Scientific reports · 2015Pooled it
- MiR-423-5p inhibition alleviates podocyte apoptosis in membranous nephropathy by targeting WT1/β-catenin axis.International urology and nephrology · 2026Article
- A TGF-β1/LEF1/β-catenin/JLP network motif regulates autophagy and tubule injury in renal fibrosis.JCI insight · 2026Article
- Chronic Aspartame Exposure Leading to Hypertension in Mice may be Related to the Activation of the Wnt/β-Catenin Signaling Pathway in the Hypothalamus.Molecular nutrition & food research · 2026Article
- Small-molecule LF3 alleviates angiotensin II-induced cardiac dysfunction via attenuating cardiac fibrosis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Hypertension-Induced Renal Injury: From Pathophysiology to Therapeutic Perspectives.Biomedicines · 2026Review
- Emerging therapeutic pipelines on kidney fibrosis: challenges in translational research.Journal of translational medicine · 2026Review
- Wnt/β-Catenin Signaling in Diabetic Complications: Mechanisms and Therapeutic Potential.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Intertwined roles of microRNA-155 and metformin in osteoarthritis: Novel potential diagnostic, prognostic, and therapeutic modulators.World journal of orthopedics · 2025Review
- Fibroblast activation and heterogeneity in fibrotic disease.Nature reviews. Nephrology · 2025Review
- Liver-Directed Gene Therapy Mitigates Early Nephropathy in Murine Glycogen Storage Disease Type Ia.Journal of inherited metabolic disease · 2025Article
- Urinary Dickkopf-related protein 3 as a novel biomarker for kidney function decline in children with Alport syndrome.Pediatric nephrology (Berlin, Germany) · 2025Article
- Renin-angiotensin system as an emerging target to modulate adult neurogenesis in health and disease.Stem cell research & therapy · 2025Review
- Update of cellular senescence in kidney fibrosis: from mechanism to potential interventions.Frontiers of medicine · 2025Review
- Poria cocos: traditional uses, triterpenoid components and their renoprotective pharmacology.Acta pharmacologica Sinica · 2025Review
- Cancer Stem Cells and the Renin-Angiotensin System in the Tumor Microenvironment of Melanoma: Implications on Current Therapies.International journal of molecular sciences · 2025Review
- Transcriptional Regulation of Lipid Metabolism by Wnt Signaling and Hox Protein Cues.Advances in experimental medicine and biology · 2025Review
- Unveiling Tirzepatide's Therapeutic Spectrum: A Dual GIP/GLP-1 Agonist Targeting Metabolic, Neurological, and Cardiovascular Health.International journal of endocrinology · 2025Review
- Genetically conditioned interaction among microRNA-155, alpha-klotho, and intra-renal RAS in male rats: Link to CKD progression.Physiological reports · 2024Article
- Collecting Duct Pro(Renin) Receptor Contributes to Unilateral Ureteral Obstruction-Induced Kidney Injury via Activation of the Intrarenal RAS.Hypertension (Dallas, Tex. : 1979) · 2024Article
96 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Activation of the renin-angiotensin system (RAS) plays an essential role in the pathogenesis of CKD and cardiovascular disease. However, current anti-RAS therapy only has limited efficacy, partly because of compensatory upregulation of renin expression. Therefore, a treatment strategy to simultaneously target multiple RAS genes is necessary to achieve greater efficacy. By bioinformatics analyses, we discovered that the promoter regions of all RAS genes contained putative T-cell factor (TCF)/lymphoid enhancer factor (LEF)-binding sites, and β-catenin induced the binding of LEF-1 to these sites in kidney tubular cells. Overexpression of either β-catenin or different Wnt ligands induced the expression of all RAS genes. Conversely, a small-molecule β-catenin inhibitor ICG-001 abolished RAS induction. In a mouse model of nephropathy induced by adriamycin, either transient therapy or late administration of ICG-001 abolished established proteinuria and kidney lesions. ICG-001 inhibited renal expression of multiple RAS genes in vivo and abolished the expression of other Wnt/β-catenin target genes. Moreover, ICG-001 therapy restored expression of nephrin, podocin, and Wilms' tumor 1, attenuated interstitial myofibroblast activation, repressed matrix expression, and inhibited renal inflammation and fibrosis. Collectively, these studies identify all RAS genes as novel downstream targets of Wnt/β-catenin. Our results indicate that blockade of Wnt/β-catenin signaling can simultaneously repress multiple RAS genes, thereby leading to the reversal of established proteinuria and kidney injury.
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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 OpenQuestion graph.