ArticleAmerican journal of respiratory cell and molecular biology2008
Prostaglandin E2 inhibits specific lung fibroblast functions via selective actions of PKA and Epac-1.
Article in American journal of respiratory cell and molecular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 125 citations in OpenAlex.
- Mechanical activation of PIEZO1 drives AP-1-dependent PTGS2/PGE2 signaling and corneal inflammation.iScience · 2026Article
- Mast cell-specific CysLT2 receptor signaling inhibits cysteinyl leukotriene-dependent mast cell activation and type 2 allergic lung inflammation.Cell reports · 2026Article
- Mechanistic basis for the antifibrotic actions of cAMP-based therapies.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Integration of cAMP and TRPV4 Signaling to Optimize Collagen Remodeling for Management of Fibrosis.Cells · 2025Review
- Loss of lung mesenchymal identities in culture and a screening approach to identify restorative cues.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Pharmacological inhibition of Epac1 protects against pulmonary fibrosis by blocking FoxO3a neddylation.The European respiratory journal · 2025Article
- Reimagining Fibrosis Research, Outcomes, and Therapeutics Through the Lens of Resolution.Seminars in respiratory and critical care medicine · 2025Review
- Distinct cAMP Regulation in Scleroderma Lung and Skin Myofibroblasts Governs Their Dedifferentiation via p38α Inhibition.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Discovering the role of microRNAs and exosomal microRNAs in chest and pulmonary diseases: a spotlight on chronic obstructive pulmonary disease.Molecular genetics and genomics : MGG · 2024Review
- Regulation of myofibroblast dedifferentiation in pulmonary fibrosis.Respiratory research · 2024Review
- Transcriptomic characterization of lung pericytes in systemic sclerosis-associated pulmonary fibrosis.iScience · 2024Article
- Novel inhalation therapy in pulmonary fibrosis: principles, applications and prospects.Journal of nanobiotechnology · 2024Review
- GPCRs and fibroblast heterogeneity in fibroblast-associated diseases.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Review
- Perspectives of PDE inhibitor on treating idiopathic pulmonary fibrosis.Frontiers in pharmacology · 2023Review
- KLF4 is a therapeutically tractable brake on fibroblast activation that promotes resolution of pulmonary fibrosis.JCI insight · 2022Article
- Prkg2 regulates alveolar type 2-mediated re-alveolarization.Stem cell research & therapy · 2022Article
- Exploration of radiation-induced lung injury, from mechanism to treatment: a narrative review.Translational lung cancer research · 2022Review
- Bortezomib Inhibits Lung Fibrosis and Fibroblast Activation without Proteasome Inhibition.American journal of respiratory cell and molecular biology · 2022Article
- Ogerin mediated inhibition of TGF-β(1) induced myofibroblast differentiation is potentiated by acidic pH.PloS one · 2022Article
- GPCR-mediated YAP/TAZ inactivation in fibroblasts via EPAC1/2, RAP2C, and MAP4K7.Journal of cellular physiology · 2021Article
28 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Via their capacities for proliferation and synthesis of matrix proteins such as collagen, fibroblasts are key effectors in the pathogenesis of fibrotic disorders such as idiopathic pulmonary fibrosis. Prostaglandin E(2) (PGE(2)) potently inhibits these functions in lung fibroblasts through receptor ligation and production of the second messenger cAMP, but the downstream pathways mediating such actions have not been fully characterized. We sought to investigate the roles of the cAMP effectors protein kinase A (PKA) and exchange protein activated by cAMP-1 (Epac-1) in modulating these two functions in primary human fetal lung IMR-90 fibroblasts. The specific roles of these two effector pathways were examined by treating cells with PKA-specific (6-bnz-cAMP) and Epac-specific (8-pCPT-2'-O-Me-cAMP) agonists, inhibiting PKA with the inhibitor KT 5720, overexpressing the PKA catalytic subunit, and silencing Epac-1 using short hairpin RNA. PGE(2) inhibition of collagen I expression was mediated exclusively by activation of PKA, while inhibition of fibroblast proliferation was mediated exclusively by activation of Epac-1. PGE(2) and Epac-1 inhibited cell proliferation through activation of the small GTPase Rap1, since decreasing Rap1 activity by transfection with Rap1GAP or the dominant-negative Rap1N17 prevented, and transfection with the constitutively active Rap1V12 mimicked, the anti-proliferative effects of PGE(2). On the other hand, PKA inhibition of collagen was dependent on inhibition of protein kinase C-delta. The selective use of PKA and Epac-1 pathways to inhibit distinct aspects of fibroblast activation illustrate the pleiotropic ability of PGE(2) to inhibit diverse fibroblast functions.
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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.