ArticleThe Journal of clinical investigation2017
Fibroblast-specific inhibition of TGF-β1 signaling attenuates lung and tumor fibrosis.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05195918 (Dose Ranging Study of Oral Epigallocatechin-3-gallate), which is not on this map. Cited by 126 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.
Dose Ranging Study of Oral Epigallocatechin-3-gallate (EGCG) Given Daily for 12 Weeks to Patients With Idiopathic Pulmonary Fibrosis (IPF) Evaluating Safety, PK Interactions With Standard of Care Drugs, and Biomarkers of Drug Effect
Who cites it
126 citing papers in PubMed, 184 citations in OpenAlex.
- A fibroblast-dependent TGF-β1/sFRP2 noncanonical Wnt signaling axis promotes epithelial metaplasia in idiopathic pulmonary fibrosis.The Journal of clinical investigation · 2024Trial
- Genome folding and nuclear speckles converge to orchestrate fibroblast activation.Science advances · 2026Article
- Hibernating bear serum triggers an anti-fibrotic signature in human fibroblasts, involving ECM remodeling and MAPK signaling activation.Scientific reports · 2026Article
- Targeting sorting nexin 3 to treat pulmonary fibrosis by dual modulating Wnt/β-catenin signaling.Cell death & disease · 2026Article
- The role of extracellular matrix stiffness in regulating fibroblast behaviors and disease progression.Frontiers in immunology · 2026Review
- Stable production of immortalized hPC-MSC-derived extracellular vesicles: integrated cargo analysis and functional validation.Stem cell research & therapy · 2025Article
- miR-146b disrupts the epidermal growth factor receptor/transforming growth factor β receptor profibrotic feedforward loop to inhibit lung fibroblast proliferation and differentiation.The Journal of pharmacology and experimental therapeutics · 2025Article
- Cancer therapy and cachexia.The Journal of clinical investigation · 2025Review
- Enhanced THBS2 promotes collagen synthesis and inflammatory secretome of fibroblasts in idiopathic pulmonary fibrosis.Scientific reports · 2025Article
- Artificial intelligence-driven discovery of YH395A: A novel TGFβR1 inhibitor with potent anti-tumor activity against triple-negative breast cancer.Cell communication and signaling : CCS · 2025Article
- Redox Mechanisms Driving Skin Fibroblast-to-Myofibroblast Differentiation.Antioxidants (Basel, Switzerland) · 2025Article
- Extracellular matrix stiffness: mechanisms in tumor progression and therapeutic potential in cancer.Experimental hematology & oncology · 2025Review
- Targeted imaging of pulmonary fibrosis by a cyclic peptide LyP-1.Scientific reports · 2025Article
- EGCG and DOX dual-drug-loaded enzyme-responsive nanovesicles boost mitochondrial-mediated ICD for improved immunotherapy.Frontiers in pharmacology · 2025Article
- Research progress on the role of biomechanical clues in the progression of lung cancer.Frontiers in cell and developmental biology · 2025Review
- Lysyl Oxidase as a Target to Reduce Graft Failure Post Solid Organ Transplantation, a Potential Target for Novel Treatment.Current medicinal chemistry · 2025Review
- Fibroblasts as a ruler of the immune microenvironment: measurement and modulation in tissue homeostasis and disease.Frontiers in immunology · 2025Review
- PI3K/Akt in IPF: untangling fibrosis and charting therapies.Frontiers in immunology · 2025Review
- Fibroblast PI3K/AKT signaling and extracellular matrix homeostasis: mechanisms, targets, and delivery challenges.Frontiers in cell and developmental biology · 2025Review
- MFAP5 as a promising biomarker for connective tissue disease-associated interstitial lung disease.Frontiers in immunology · 2025Article
66 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
TGF-β1 signaling is a critical driver of collagen accumulation and fibrotic disease but also a vital suppressor of inflammation and epithelial cell proliferation. The nature of this multifunctional cytokine has limited the development of global TGF-β1 signaling inhibitors as therapeutic agents. We conducted phenotypic screens for small molecules that inhibit TGF-β1-induced epithelial-mesenchymal transition without immediate TGF-β1 receptor (TβR) kinase inhibition. We identified trihydroxyphenolic compounds as potent blockers of TGF-β1 responses (IC50 ~50 nM), Snail1 expression, and collagen deposition in vivo in models of pulmonary fibrosis and collagen-dependent lung cancer metastasis. Remarkably, the functional effects of trihydroxyphenolics required the presence of active lysyl oxidase-like 2 (LOXL2), thereby limiting effects to fibroblasts or cancer cells, the major LOXL2 producers. Mechanistic studies revealed that trihydroxyphenolics induce auto-oxidation of a LOXL2/3-specific lysine (K731) in a time-dependent reaction that irreversibly inhibits LOXL2 and converts the trihydrophenolic to a previously undescribed metabolite that directly inhibits TβRI kinase. Combined inhibition of LOXL2 and TβRI activities by trihydrophenolics resulted in potent blockade of pathological collagen accumulation in vivo without the toxicities associated with global inhibitors. These findings elucidate a therapeutic approach to attenuate fibrosis and the disease-promoting effects of tissue stiffness by specifically targeting TβRI kinase in LOXL2-expressing cells.
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What OpenQuestion 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 OpenQuestion graph.