ArticleThe Journal of biological chemistry2012
Axin pathway activity regulates in vivo pY654-β-catenin accumulation and pulmonary fibrosis.
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.
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Who cites it
49 citing papers in PubMed, 85 citations in OpenAlex.
- Paracrine activation of WNT/β-catenin pathway in uterine leiomyoma stem cells promotes tumor growth.Proceedings of the National Academy of Sciences of the United States of America · 2013Trial
- A WNT mimetic with broad spectrum FZD-specificity decreases fibrosis and improves function in a pulmonary damage model.Respiratory research · 2024Article
- Tankyrase inhibition interferes with junction remodeling, induces leakiness, and disturbs YAP1/TAZ signaling in the endothelium.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Review
- The Molecular Mechanisms of Systemic Sclerosis-Associated Lung Fibrosis.International journal of molecular sciences · 2023Review
- Saracatinib, a Selective Src Kinase Inhibitor, Blocks Fibrotic Responses in Preclinical Models of Pulmonary Fibrosis.American journal of respiratory and critical care medicine · 2022Article
- Axin1: A novel scaffold protein joins the antiviral network of interferon.Molecular microbiology · 2022Article
- Phosphorylation-Dependent Regulation of WNT/Beta-Catenin Signaling.Frontiers in oncology · 2022Review
- Targeting Growth Factor and Cytokine Pathways to Treat Idiopathic Pulmonary Fibrosis.Frontiers in pharmacology · 2022Review
- WNT Signalling in Lung Physiology and Pathology.Handbook of experimental pharmacology · 2021Article
- Yap1 is required for maintenance of adult RPE differentiation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Alveolar Epithelial Type II Cells as Drivers of Lung Fibrosis in Idiopathic Pulmonary Fibrosis.International journal of molecular sciences · 2020Review
- Therapeutic molecular targets of SSc-ILD.Journal of scleroderma and related disorders · 2020Article
- Involvement of TGF-β and Autophagy Pathways in Pathogenesis of Diabetes: A Comprehensive Review on Biological and Pharmacological Insights.Frontiers in pharmacology · 2020Review
- Nintedanib Inhibits Wnt3a-Induced Myofibroblast Activation by Suppressing the Src/β-Catenin Pathway.Frontiers in pharmacology · 2020Article
- Tankyrase (PARP5) Inhibition Induces Bone Loss through Accumulation of Its Substrate SH3BP2.Cells · 2019Review
- A regulatory loop connecting WNT signaling and telomere capping: possible therapeutic implications for dyskeratosis congenita.Annals of the New York Academy of Sciences · 2018Review
- Pharmacological inhibition of tankyrase induces bone loss in mice by increasing osteoclastogenesis.Bone · 2018Article
- Nintedanib reduces ventilation-augmented bleomycin-induced epithelial-mesenchymal transition and lung fibrosis through suppression of the Src pathway.Journal of cellular and molecular medicine · 2017Article
- Characterization of age-related penile microvascular hemodynamic impairment using laser speckle contrast imaging: possible role of increased fibrogenesis.Physiological reports · 2017Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Epithelial to mesenchymal transition (EMT) and pulmonary fibrogenesis require epithelial integrin α3β1-mediated cross-talk between TGFβ1 and Wnt signaling pathways. One hallmark of this cross-talk is pY654-β-catenin accumulation, but whether pY654-β-catenin is a biomarker of fibrogenesis or functionally important is unknown. To clarify further the role of β-catenin in fibrosis, we explored pY654-β-catenin generation and function. α3β1 was required for TGFβ1-mediated activation of Src family kinases, and Src inhibition blocked both pY654 and EMT in primary alveolar epithelial cells (AECs). TGFβ1 stimulated β-catenin/Lef1-dependent promoter activity comparably in immortalized AECs stably expressing WT β-catenin as well as Y654E or Y654F β-catenin point mutants. But EMT was abrogated in the Tyr to Phe mutant. pY654-β-catenin was sensitive to the axin β-catenin turnover pathway as inhibition of tankyrase 1 led to high AEC axin levels, loss of pY654-β-catenin, and inhibition of EMT ex vivo. Mice given a tankyrase inhibitor (50 mg/kg orally) daily for 7 days beginning 10 days after intratracheal bleomycin had improved survival over controls. Treated mice developed raised axin levels in the lung that abrogated pY654-β-catenin and attenuated lung Snail1, Twist1, α-smooth muscle actin, and type I collagen accumulation. Total β-catenin levels were unaltered. These findings identify Src kinase(s) as a mediator of TGFβ1-induced pY654-β-catenin, provide evidence that pY654-β-catenin levels are a critical determinant of EMT and fibrogenesis, and suggest regulation of axin levels as a novel therapeutic approach to fibrotic disorders.
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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.