ArticleThe Journal of biological chemistry2014
Glucocorticoids recruit Tgfbr3 and Smad1 to shift transforming growth factor-β signaling from the Tgfbr1/Smad2/3 axis to the Acvrl1/Smad1 axis in lung fibroblasts.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 80 citations in OpenAlex.
- Exploring TGFBR3 in disease pathogenesis: Mechanisms, clinical implications, and pharmacological modulation.Journal of pharmaceutical analysis · 2026Review
- The rise and fall of glucocorticoids and immunosuppressants in idiopathic pulmonary fibrosis: a historical paradigm shift driven by mechanistic understanding.Frontiers in immunology · 2026Review
- Acute Shear Stress Induces TWIST-Mediated EndMT in Venous Endothelial Cells and Human Long Saphenous Veins.Cells · 2025Article
- Delineating Effects of Stress-Analogous, Low-Dose Cortisol Exposure on Human Vocal Fold Fibroblasts.Journal of voice : official journal of the Voice Foundation · 2025Article
- Study on the changes of extracellular matrix morphology and components in COPD animal model by using lung decellularized scaffold.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- FBLN7 KO attenuates age-related cardiac fibrosis by promoting TGFBR3/ALK1/Smad1 signaling and inhibiting the profibrotic phenotypes of cardiac fibroblasts.Theranostics · 2025Article
- Screening of Phytocompounds Against the NF-kB Pathway Genes and Lung Elevated Proteins Associated with Acute Respiratory Distress Syndrome.Recent advances in inflammation & allergy drug discovery · 2025Article
- Leveraging DNA methylation to create Epigenetic Biomarker Proxies that inform clinical care: A new framework for Precision Medicine.medRxiv : the preprint server for health sciences · 2024Article
- Nasal allergen and methacholine provocation tests influence co‑expression patterns of TGF‑β/SMAD and MAPK signaling pathway genes in patients with asthma.Experimental and therapeutic medicine · 2024Article
- Molar Incisor Hypomineralization: Etiology, Correlation with Tooth Number Anomalies and Implications for Comprehensive Management Strategies in Children from Transylvania.Diagnostics (Basel, Switzerland) · 2024Article
- Enhanced fibrotic potential of COL1A1Frontiers in cardiovascular medicine · 2024Article
- Opposing roles for TGFβ- and BMP-signaling during nascent alveolar differentiation in the developing human lung.NPJ Regenerative medicine · 2023Article
- Complex roles of TGF-β signaling pathways in lung development and bronchopulmonary dysplasia.American journal of physiology. Lung cellular and molecular physiology · 2023Review
- Differential CpG DNA methylation of peripheral B cells, CD4Arthritis research & therapy · 2023Article
- Glucocorticoid Effects on Proteoglycans and Glycosaminoglycans.International journal of molecular sciences · 2022Review
- Transforming growth factor-β in myocardial disease.Nature reviews. Cardiology · 2022Review
- Article
- Asthmatic Eosinophils Alter the Gene Expression of Extracellular Matrix Proteins in Airway Smooth Muscle Cells and Pulmonary Fibroblasts.International journal of molecular sciences · 2022Article
- Elevated IgE promotes cardiac fibrosis by suppressing miR-486a-5p.Theranostics · 2021Article
- The role of Smad signaling cascades in cardiac fibrosis.Cellular signalling · 2021Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glucocorticoids represent the mainstay therapy for many lung diseases, providing outstanding management of asthma but performing surprisingly poorly in patients with acute respiratory distress syndrome, chronic obstructive pulmonary disease, lung fibrosis, and blunted lung development associated with bronchopulmonary dysplasia in preterm infants. TGF-β is a pathogenic mediator of all four of these diseases, prompting us to explore glucocorticoid/TGF-β signaling cross-talk. Glucocorticoids, including dexamethasone, methylprednisolone, budesonide, and fluticasone, potentiated TGF-β signaling by the Acvrl1/Smad1/5/8 signaling axis and blunted signaling by the Tgfbr1/Smad2/3 axis in NIH/3T3 cells, as well as primary lung fibroblasts, smooth muscle cells, and endothelial cells. Dexamethasone drove expression of the accessory type III TGF-β receptor Tgfbr3, also called betaglycan. Tgfbr3 was demonstrated to be a "switch" that blunted Tgfbr1/Smad2/3 and potentiated Acvrl1/Smad1 signaling in lung fibroblasts. The Acvrl1/Smad1 axis, which was stimulated by dexamethasone, was active in lung fibroblasts and antagonized Tgfbr1/Smad2/3 signaling. Dexamethasone acted synergistically with TGF-β to drive differentiation of primary lung fibroblasts to myofibroblasts, revealed by acquisition of smooth muscle actin and smooth muscle myosin, which are exclusively Smad1-dependent processes in fibroblasts. Administration of dexamethasone to live mice recapitulated these observations and revealed a lung-specific impact of dexamethasone on lung Tgfbr3 expression and phospho-Smad1 levels in vivo. These data point to an interesting and hitherto unknown impact of glucocorticoids on TGF-β signaling in lung fibroblasts and other constituent cell types of the lung that may be relevant to lung physiology, as well as lung pathophysiology, in terms of drug/disease interactions.
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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.