ArticleTranslational research : the journal of laboratory and clinical medicine2023
Nedd4L suppression in lung fibroblasts facilitates pathogenesis of lung fibrosis.
Article in Translational research : the journal of laboratory and clinical medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- E3 ligase SMURF2 promotes adipogenesis and improves obesity complications by suppressing TGF-β signaling.Journal of lipid research · 2026Article
- NEDD4L knockdown enhances synovial fibroblast migration, invasion, and inflammatory factor secretion via Wnt/β-Catenin signaling activation.Clinical rheumatology · 2026Article
- The role of HECT-type E3 ubiquitin ligases in inflammation.Frontiers in immunology · 2026Review
- TRIM36 inhibits lung fibroblast activation and pulmonary fibrosis through the degradation of phospho-AKT1.iScience · 2025Article
- Nedd4L signaling contributes to carbon tetrachloride-induced liver fibrosis in female mice and is associated with enteric dysbacteriosis.Gastroenterology report · 2025Article
- Targeting E3 ubiquitin ligases: a new frontier in idiopathic pulmonary fibrosis treatment.Frontiers in immunology · 2025Review
- Longitudinal microcomputed tomography detects onset and progression of pulmonary fibrosis in conditionalAmerican journal of physiology. Lung cellular and molecular physiology · 2024Article
- NEDD4 and NEDD4L: Ubiquitin Ligases Closely Related to Digestive Diseases.Biomolecules · 2024Review
- Molecular Regulation of Transforming Growth Factor-β1-induced Thioredoxin-interacting Protein Ubiquitination and Proteasomal Degradation in Lung Fibroblasts: Implication in Pulmonary Fibrosis.Journal of respiratory biology and translational medicine · 2024Article
- The Upregulation of Leucine-Rich Repeat Containing 1 Expression Activates Hepatic Stellate Cells and Promotes Liver Fibrosis by Stabilizing Phosphorylated Smad2/3.International journal of molecular sciences · 2024Article
- circGRHPR inhibits aberrant epithelial-mesenchymal transformation progression of lung epithelial cells associated with idiopathic pulmonary fibrosis.Cell biology and toxicology · 2024Article
- Article
- GGA (geranylgeranylacetone) ameliorates bleomycin-induced lung inflammation and pulmonary fibrosis by inhibiting apoptosis and oxidative stress.Molecular biology reports · 2023Article
- NEDD4L in human tumors: regulatory mechanisms and dual effects on anti-tumor and pro-tumor.Frontiers in pharmacology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Ubiquitination-mediated protein degradation is associated with the development of pulmonary fibrosis. We and others have shown that Nedd4L plays anti-inflammatory and anti-fibrotic roles by targeting lysophosphatidic acid receptor 1 (LPAR1), p-Smad2/3, and β-catenin, and other molecules for their degradation in lung epithelial cells and fibroblasts. However, the molecular regulation of Nedd4L expression in lung fibroblasts has not been studied. In this study, we find that Nedd4L levels are significantly suppressed in lung myofibroblasts in IPF patients and in experimental pulmonary fibrosis, and in TGF-β1-treated lung fibroblasts. Nedd4L knockdown promotes TGF-β1-mediated phosphorylation of Smad2/3 and lung myofibroblast differentiation. Mechanistically, Nedd4L targets TGF-β receptor II (TβRII), the first key enzyme of TGF-β1-mediated signaling, for its ubiquitination and degradation. Further, we show that inhibition of transcriptional factor E2F rescues Nedd4L levels and mitigates experimental pulmonary fibrosis. Together, our data reveal insight into mechanisms by which E2F-mediated Nedd4L suppression contributes to the pathogenesis of lung fibrosis. This study provides evidence showing that upregulation of Nedd4L is a potential therapeutic strategy to treat fibrotic disorders including lung fibrosis.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.