ArticleActa pharmacologica Sinica2024
E3 ubiquitin ligase NEDD4L inhibits epithelial-mesenchymal transition by suppressing the β-catenin/HIF-1α positive feedback loop in chronic rhinosinusitis with nasal polyps.
Article in Acta pharmacologica Sinica, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.
- Neurobiological mechanisms of olfactory dysfunction: a ten-year bibliometric and visualization analysis.Frontiers in medicine · 2026Pooled it
- The SPRR2A-CSTA axis drives IL-17A-induced squamous metaplasia and steroid resistance in allergic rhinitis.The Journal of allergy and clinical immunology · 2026Article
- NEDD4L knockdown enhances synovial fibroblast migration, invasion, and inflammatory factor secretion via Wnt/β-Catenin signaling activation.Clinical rheumatology · 2026Article
- Inflammatory Shift in Chronic Rhinosinusitis Amidst Guangzhou's Urbanization (2000-2018).World journal of otorhinolaryngology - head and neck surgery · 2026Article
- Identification of DIO2 as a Molecular Therapeutic Target for Depression in Chronic Rhinosinusitis: A Comprehensive Bioinformatics and Experimental Study.Biochemical genetics · 2026Article
- Hypoxia: a critical pathophysiological driver in respiratory inflammatory diseases.Military Medical Research · 2026Review
- Exploring the Potential Value of Inflammatory Response-Associated Genes in Chronic Rhinosinusitis with Nasal Polyps: An Integrated Bioinformatics and Experimental Validation Analysis.Journal of inflammation research · 2026Article
- Neurotensin receptor1 signaling promotes progression of epithelial-mesenchymal transition in mice with chronic rhinosinusitis through Wnt3a/β-catenin pathway.Journal of molecular histology · 2025Article
- [Mechanisms of HNE mediated NLRP3 promoting EMT in chronic rhinosinusitis with polyps].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2025Article
- LncRNA NEAT1 promotes epithelial-mesenchymal transition in nasal polyp cells via the miR-199-3p/PAK4 axis.Frontiers in immunology · 2025Article
- Role of Ubiquitin-regulated EMT in Cancer Metastasis and Chemoresistance.International journal of biological sciences · 2025Review
- NEDD4L Suppresses Proliferation and Promotes Apoptosis by Ubiquitinating RAC2 Expression and Acts as a Prognostic Biomarker in Clear Cell Renal Cell Carcinoma.International journal of molecular sciences · 2024Article
- Epithelial-Mesenchymal Transition in Chronic Rhinosinusitis.Journal of rhinology : official journal of the Korean Rhinologic Society · 2024Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic rhinosinusitis with nasal polyp (CRSwNP) is a refractory inflammatory disease with epithelial-mesenchymal transition (EMT) as one of the key features. Since ubiquitin modification has been shown to regulate the EMT process in other diseases, targeting ubiquitin ligases may be a potential strategy for the treatment of CRSwNP. In this study we investigated whether certain E3 ubiquitin ligases could regulate the EMT process in CRSwNP, and whether these regulations could be the potential drug targets as well as the underlying mechanisms. After screening the potential drug target by bioinformatic analyses, the expression levels of three potential E3 ubiquitin ligases were compared among the control, eosinophilic nasal polyp (ENP) and non-eosinophilic nasal polyp (NENP) group in clinical samples, and the significant decrement of the expression level of NEDD4L was found. Then, IP-MS, bioinformatics and immunohistochemistry studies suggested that low NEDD4L expression may be associated with the EMT process. In human nasal epithelial cells (hNECs) and human nasal epithelial cell line RPMI 2650, knockdown of NEDD4L promoted EMT, while upregulating NEDD4L reversed this effect, suggesting that NEDD4L inhibited EMT in nasal epithelial cells. IP-MS and Co-IP studies revealed that NEDD4L mediated the degradation of DDR1. We demonstrated that NEDD4L inhibited the β-catenin/HIF-1α positive feedback loop either directly (degrading β-catenin and HIF-1α) or indirectly (mediating DDR1 degradation). These results were confirmed in a murine NP model in vivo. This study for the first time reveals the regulatory role of ubiquitin in the EMT process of nasal epithelial cells, and identifies a novel drug target NEDD4L, which has promising efficacy against both ENP and NENP by suppressing β-catenin/HIF-1α positive feedback loop.
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