ArticleJournal of the American Society of Nephrology : JASN2015
Mutual antagonism of Wilms' tumor 1 and β-catenin dictates podocyte health and disease.
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 41 papers.
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Who cites it
41 citing papers in PubMed, 66 citations in OpenAlex.
- MiR-423-5p inhibition alleviates podocyte apoptosis in membranous nephropathy by targeting WT1/β-catenin axis.International urology and nephrology · 2026Article
- Wnt/β-Catenin Signaling in Diabetic Complications: Mechanisms and Therapeutic Potential.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Axial nephron fate switching demonstrates a plastic system tunable on demand.Nature communications · 2025Article
- Unveiling Tirzepatide's Therapeutic Spectrum: A Dual GIP/GLP-1 Agonist Targeting Metabolic, Neurological, and Cardiovascular Health.International journal of endocrinology · 2025Review
- Gene regulatory networks in disease and ageing.Nature reviews. Nephrology · 2024Review
- Blockade of Notch1 Signaling Alleviated Podocyte Injury in Lupus Nephritis Via Inhibition of NLRP3 Inflammasome Activation.Inflammation · 2024Article
- Evaluation of glomerular sirtuin-1 and claudin-1 in the pathophysiology of nondiabetic focal segmental glomerulosclerosis.Scientific reports · 2023Article
- Pathomechanisms of Diabetic Kidney Disease.Journal of clinical medicine · 2023Review
- Endothelial Dysfunction in Cardiorenal Conditions: Implications of Endothelial Glucocorticoid Receptor-Wnt Signaling.International journal of molecular sciences · 2023Review
- Sirtuin 6 is a key contributor to gender differences in acute kidney injury.Cell death discovery · 2023Article
- Klotho's impact on diabetic nephropathy and its emerging connection to diabetic retinopathy.Frontiers in endocrinology · 2023Review
- B7-1 mediates podocyte injury and glomerulosclerosis through communication with Hsp90ab1-LRP5-β-catenin pathway.Cell death and differentiation · 2022Article
- Podocyte specific deletion of PKM2 ameliorates LPS-induced podocyte injury through beta-catenin.Cell communication and signaling : CCS · 2022Article
- β-catenin-controlled tubular cell-derived exosomes play a key role in fibroblast activation via the OPN-CD44 axis.Journal of extracellular vesicles · 2022Article
- High Fat Diet Induces Kidney InjuryFrontiers in medicine · 2022Article
- Article
- The recruitment mechanisms and potential therapeutic targets of podocytes from parietal epithelial cells.Journal of translational medicine · 2021Review
- Article
- Role of miRNA-671-5p in Mediating Wnt/β-Catenin-Triggered Podocyte Injury.Frontiers in pharmacology · 2021Article
- Constitutive activation of CTNNB1 results in a loss of spermatogonial stem cell activity in mice.PloS one · 2021Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Activation of β-catenin, the intracellular mediator of canonical Wnt signaling, has a critical role in mediating podocyte injury and proteinuria. However, the underlying mechanisms remain poorly understood. Here, we show that β-catenin triggers ubiquitin-mediated protein degradation of Wilms' tumor 1 (WT1) and functionally antagonizes its action. In mice injected with adriamycin, WT1 protein was progressively lost in glomerular podocytes at 1, 3, and 5 weeks after injection. Notably, loss of WT1 apparently did not result from podocyte depletion but was closely associated with upregulation of β-catenin. This change in WT1/β-catenin ratio was accompanied by loss of podocyte-specific nephrin, podocalyxin, and synaptopodin and acquisition of mesenchymal markers Snail1, α-smooth muscle actin, and fibroblast-specific protein 1. In vitro, overexpression of β-catenin induced WT1 protein degradation through the ubiquitin proteasomal pathway, which was blocked by MG-132. WT1 and β-catenin also competed for binding to common transcriptional coactivator CREB-binding protein and mutually repressed the expression of their respective target genes. In glomerular miniorgan culture, activation of β-catenin by Wnt3a repressed WT1 and its target gene expression. In vivo, blockade of Wnt/β-catenin signaling by endogenous antagonist Klotho induced WT1 and restored podocyte integrity in adriamycin nephropathy. These results show that β-catenin specifically targets WT1 for ubiquitin-mediated degradation, leading to podocyte dedifferentiation and mesenchymal transition. Our data also suggest that WT1 and β-catenin have opposing roles in podocyte biology, and that the ratio of their expression levels dictates the state of podocyte health and disease in vivo.
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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.