ArticleThe American journal of pathology2001
Cyclooxygenase-2 deficiency results in a loss of the anti-proliferative response to transforming growth factor-beta in human fibrotic lung fibroblasts and promotes bleomycin-induced pulmonary fibrosis in mice.
Article in The American journal of pathology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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Who cites it
102 citing papers in PubMed, 245 citations in OpenAlex.
- Matrices of physiologic stiffness potently inactivate idiopathic pulmonary fibrosis fibroblasts.American journal of respiratory cell and molecular biology · 2013Trial
- Decoding Dysregulation of DNA Methylation in Epigenetics of Idiopathic Pulmonary Fibrosis.Canadian respiratory journal · 2026Review
- Global deletion of COX-2 attenuates hepatic inflammation but impairs metabolic homeostasis in diet-induced obesity.Journal of lipid research · 2025Article
- A Redox-Shifted Fibroblast Subpopulation Emerges in the Fibrotic Lung.American journal of respiratory cell and molecular biology · 2024Article
- Erythropoietin Reduces Inflammation, Oxidative Stress, and Apoptosis in a Rat Model of Bleomycin-Induced Idiopathic Pulmonary Fibrosis.Journal of personalized medicine · 2024Article
- RNA-sequencing reveals differential fibroblast responses to bleomycin and pneumonectomy.Physiological reports · 2024Article
- Transcriptomic characterization of lung pericytes in systemic sclerosis-associated pulmonary fibrosis.iScience · 2024Article
- Lung extracellular matrix modulates KRT5Nature communications · 2023Article
- Fibrosis-the tale of H3K27 histone methyltransferases and demethylases.Frontiers in cell and developmental biology · 2023Review
- Article
- 3D In Vitro Models: Novel Insights into Idiopathic Pulmonary Fibrosis Pathophysiology and Drug Screening.Cells · 2022Review
- Inhibiting collagen I production and tumor cell colonization in the lungActa pharmaceutica Sinica. B · 2022Article
- Antifibrotic effects of Quercetin on TGF-β1-induced vocal fold fibroblasts.American journal of translational research · 2022Article
- Modulation of COX-2 and NADPH oxidase-4 by alpha-lipoic acid ameliorates busulfan-induced pulmonary injury in rats.Heliyon · 2021Article
- Enzymes Present in Neutrophil Extracellular Traps May Stimulate the Fibrogenic PGFAnimals : an open access journal from MDPI · 2021Article
- Expression of serum response factor in the lung mesenchyme is essential for development of pulmonary fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- ReducedBiomedicines · 2021Article
- Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis.Cellular and molecular life sciences : CMLS · 2021Review
- The Downregulation of PTGS2 Mediated by ncRNAs is Tightly Correlated with Systemic Sclerosis-Interstitial Lung Disease.Frontiers in genetics · 2021Article
- mTORC1 amplifies the ATF4-dependent de novo serine-glycine pathway to supply glycine during TGF-βScience signaling · 2019Article
42 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Prostaglandin E(2) (PGE(2)) inhibits fibroblast proliferation and collagen production. Its synthesis by fibroblasts is induced by profibrotic mediators including transforming growth factor (TGF)-beta(1). However, in patients with pulmonary fibrosis, PGE(2) levels are decreased. In this study we examined the effect of TGF-beta(1) on PGE(2) synthesis, proliferation, collagen production, and cyclooxygenase (COX) mRNA levels in fibroblasts derived from fibrotic and nonfibrotic human lung. In addition, we examined the effect of bleomycin-induced pulmonary fibrosis in COX-2-deficient mice. We demonstrate that basal and TGF-beta(1)-induced PGE(2) synthesis is limited in fibroblasts from fibrotic lung. Functionally, this correlates with a loss of the anti-proliferative response to TGF-beta(1). This failure to induce PGE(2) synthesis is because of an inability to up-regulate COX-2 mRNA levels in these fibroblasts. Furthermore, mice deficient in COX-2 exhibit an enhanced response to bleomycin. We conclude that a decreased capacity to up-regulate COX-2 expression and COX-2-derived PGE(2) synthesis in the presence of increasing levels of profibrotic mediators such as TGF-beta(1) may lead to unopposed fibroblast proliferation and collagen synthesis and contribute to the pathogenesis of pulmonary fibrosis.
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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.