Trial reportThe Journal of clinical investigation2024
A fibroblast-dependent TGF-β1/sFRP2 noncanonical Wnt signaling axis promotes epithelial metaplasia in idiopathic pulmonary fibrosis.
Trial report in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
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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
54 citing papers in PubMed.
- Efficacy and safety of 7-day aerosolized epigallocatechin-3-gallate in oncologic patients with COVID-19 pneumonia.BMC cancer · 2026Trial
- Integrated Bioinformatics and Experimental Validation to Identify Shared Sialylation-Related Signatures in Emphysematous and Fibrotic Lung Disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- CUDC-907 attenuates pulmonary fibrosis by reversing HDAC1-mediated SMAD4 deacetylation at lysine 45.Biology direct · 2026Article
- Multi-omics insights into the mechanisms and prognosis of IPF.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2026Review
- Activation of ERBB4 Pathway Inhibits Pathological Transdifferentiation of Lung Epithelial Progenitors into CD66cAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Epigenetic de-repression of basal cell metaplasia in aging AT2 cells is a risk factor for idiopathic pulmonary fibrosis (IPF).bioRxiv : the preprint server for biology · 2026Article
- Article
- Effects of the WNT signaling pathway on inflammation and fibrosis in idiopathic pulmonary fibrosis: Clinical, radiological and molecular evaluation.Experimental and therapeutic medicine · 2026Article
- Spatial Distribution of K13-Positive Airway Epithelial Cells in Idiopathic Pulmonary Fibrosis.Biomedicines · 2026Article
- miR-214-3p Mediates Samarium Oxide-Induced Pulmonary Fibrosis by Targeting MAP2K3 via the MAPK Signaling Pathway.Toxics · 2026Article
- Decoding organ fibrosis: mechanistic insights and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Multi-Omic and Single-Cell Approaches for Elucidating Cell Biology and Pathobiology of Lung Disease.American journal of respiratory cell and molecular biology · 2026Review
- Human iPSC-based Modeling of Pulmonary Fibrosis Reveals p300/CBP Inhibition Suppresses Alveolar Transitional Cell State.Nature communications · 2026Article
- Wnt11 mediates fibroblast-smooth muscle cell interaction to promote neurogenic bladder fibrosis in rats.Communications biology · 2026Article
- Hypoxia-Driven Pulmonary Adaptation in the Yak: A Homeostatic Mechanism Mediated by Cell Adhesion Molecules.International journal of molecular sciences · 2026Article
- Research Advances and Disease Modeling in Respiratory Organoids.Biomedicines · 2026Review
- Inhibition of CDK8 rescues impaired ischemic fracture healing.NPJ Regenerative medicine · 2026Article
- Molecular mechanisms and network interactions in radiation-induced lung injury.Frontiers in physiology · 2026Review
- An hiPSC-derived multi-lineage lung model exhibiting proximal-distal epithelial features for modeling pulmonary fibrosis.Frontiers in cell and developmental biology · 2026Article
- Temporal regulation of wnt signaling in alveolar development and regeneration: mechanistic insights and therapeutic advances in chronic lung diseases.Frontiers in cell and developmental biology · 2026Review
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Reciprocal interactions between alveolar fibroblasts and epithelial cells are crucial for lung homeostasis, injury repair, and fibrogenesis, but underlying mechanisms remain unclear. To investigate, we administered the fibroblast-selective TGF-β1 signaling inhibitor epigallocatechin gallate (EGCG) to interstitial lung disease (ILD) patients undergoing diagnostic lung biopsy and conducted single-cell RNA-Seq on spare tissue. Biopsies from untreated patients showed higher fibroblast TGF-β1 signaling compared with nondisease donor or end-stage ILD tissues. In vivo, EGCG downregulated TGF-β1 signaling and several proinflammatory and stress pathways in biopsy samples. Notably, EGCG reduced fibroblast secreted frizzled-related protein 2 (sFRP2), an unrecognized TGF-β1 fibroblast target gene induced near type II alveolar epithelial cells (AEC2s) in situ. Using AEC2-fibroblast coculture organoids and precision-cut lung slices (PCLSs) from nondiseased donors, we found TGF-β1 signaling promotes a spread AEC2 KRT17+ basaloid state, whereupon sFRP2 then activates a mature cytokeratin 5+ (Krt5+) basal cell program. Wnt-receptor Frizzled 5 (Fzd5) expression and downstream calcineurin signaling were required for sFRP2-induced nuclear NFATc3 accumulation and KRT5 expression. These findings highlight stage-specific TGF-β1 signaling in ILD and the therapeutic potential of EGCG in reducing idiopathic pulmonary fibrosis-related (IPF-related) transcriptional changes and identify TGF-β1/noncanonical Wnt pathway crosstalk via sFRP2 as a mechanism for dysfunctional epithelial signaling in IPF/ILD.
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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.