ArticleThe Journal of biological chemistry2012
Activation of Wnt11 by transforming growth factor-β drives mesenchymal gene expression through non-canonical Wnt protein signaling in renal epithelial cells.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 2 of them syntheses that pooled it.
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Who cites it
49 citing papers in PubMed, 2 syntheses or guidelines pooled it, 70 citations in OpenAlex.
- Differential expression of members of SOX family of transcription factors in failing human hearts.Translational research : the journal of laboratory and clinical medicine · 2022Pooled it
- Systematic analysis of metastasis-associated genes identifies miR-17-5p as a metastatic suppressor of basal-like breast cancer.Breast cancer research and treatment · 2014Pooled it
- Non-Canonical Wnt11 Signaling Regulates Pulmonary Fibrosis via Fibroblast and Alveolar Epithelial Type II Cell Crosstalk.International journal of molecular sciences · 2025Article
- Inflammation in cardiovascular-kidney-metabolic syndrome: key roles and underlying mechanisms-a comprehensive review.Molecular and cellular biochemistry · 2025Review
- The Dual Role and Therapeutic Implications of the Wnt/β-Catenin Pathway in Diabetic Kidney Disease.International journal of general medicine · 2025Review
- Genome-wide CRISPR/Cas9 screening identifies key profibrotic regulators of TGF-β1-induced epithelial-mesenchymal transformation and pulmonary fibrosis.Frontiers in molecular biosciences · 2025Article
- Biliary atresia: insights into mechanisms using a toxic model of the disease including Wnt and Hippo signaling pathways and microtubules.Pediatric research · 2025Article
- Noncanonical WNT5A controls the activation of latent TGF-β to drive fibroblast activation and tissue fibrosis.The Journal of clinical investigation · 2024Article
- Renal-specific loss of ferroportin disrupts iron homeostasis and attenuates recovery from acute kidney injury.American journal of physiology. Renal physiology · 2024Article
- Deletion of STAT3 from Foxd1 cell population protects mice from kidney fibrosis by inhibiting pericytes trans-differentiation and migration.Cell reports · 2022Article
- Noncanonical Wnt Signaling Promotes Myofibroblast Differentiation in Pulmonary Fibrosis.American journal of respiratory cell and molecular biology · 2021Article
- Cardiac Wnt5a and Wnt11 promote fibrosis by the crosstalk of FZD5 and EGFR signaling under pressure overload.Cell death & disease · 2021Article
- Applications and therapeutic mechanisms of action of mesenchymal stem cells in radiation-induced lung injury.Stem cell research & therapy · 2021Review
- WNT-β-catenin signalling - a versatile player in kidney injury and repair.Nature reviews. Nephrology · 2021Review
- Low-density lipoprotein receptor-related protein 6 regulates cardiomyocyte-derived paracrine signaling to ameliorate cardiac fibrosis.Theranostics · 2021Article
- Signaling Pathways Involved in Diabetic Renal Fibrosis.Frontiers in cell and developmental biology · 2021Review
- Inhibition on JNK Mimics Silencing of Wnt-11 Mediated Cellular Response in Androgen-Independent Prostate Cancer Cells.Biology · 2020Article
- Non-canonical WNT5a regulates Epithelial-to-Mesenchymal Transition in the mouse ovarian surface epithelium.Scientific reports · 2020Article
- Pax2 and Pax8 Proteins Regulate Urea Transporters and Aquaporins to Control Urine Concentration in the Adult Kidney.Journal of the American Society of Nephrology : JASN · 2020Article
- Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Transforming growth factor β1 (TGF-β) promotes renal interstitial fibrosis in vivo and the expression of mesenchymal genes in vitro; however, most of its direct targets in epithelial cells are still elusive. In a screen for genes directly activated by TGF-β, we found that components of the Wnt signaling pathway, especially Wnt11, were targets of activation by TGF-β and Smad3 in primary renal epithelial cells. In gain and loss of function experiments, Wnt11 mediated the actions of TGF-β through enhanced activation of mesenchymal marker genes, such as Zeb1, Snail1, Pai1, and αSMA, without affecting Smad3 phosphorylation. Inhibition of Wnt11 by receptor knockdown or treatment with Wnt inhibitors limited the effects of TGF-β on gene expression. We found no evidence that Wnt11 activated the canonical Wnt signaling pathway in renal epithelial cells; rather, the function of Wnt11 was mediated by the c-Jun N-terminal kinase (JNK) pathway. Consistent with the in vitro results, all the TGF-β, Wnt11, and JNK targets were activated in a unilateral ureteral obstruction (UUO) model of renal fibrosis in vivo. Our findings demonstrated cooperativity among the TGF-β, Wnt11, and JNK signaling pathways and suggest new targets for anti-fibrotic therapy in renal tissue.
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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.