ArticleThe Journal of biological chemistry2010
Increased cAMP levels modulate transforming growth factor-beta/Smad-induced expression of extracellular matrix components and other key fibroblast effector functions.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 83 citations in OpenAlex.
- Roflumilast Inhibits Fibrogenic Activation in Human Intestinal Myofibroblasts via Inhibition of Myocardin-Related Transcription Factor/Serum Response Factor Signaling.International journal of molecular sciences · 2026Article
- Novel Role for CGRP in Aqueous Humor Outflow.Investigative ophthalmology & visual science · 2026Article
- Deacetylforskolin ameliorates bleomycin-induced pulmonary fibrosis by suppressing inflammation and TGF-β1-induced epithelial-mesenchymal transition.Natural products and bioprospecting · 2026Article
- Comprehensive analysis of proteomics and lactylation proteomics in ovarian granulosa cells of patients with polycystic ovary syndrome.Clinical proteomics · 2026Article
- Microglial Deletion of Hrh4 Alleviates Alzheimer's Disease Pathologies by Enhancing Microglial Phagocytosis of Amyloid-β and Tau.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integration of cAMP and TRPV4 Signaling to Optimize Collagen Remodeling for Management of Fibrosis.Cells · 2025Review
- Insights into the Cellular and Molecular Mechanisms behind the Antifibrotic Effects of Nerandomilast.American journal of respiratory cell and molecular biology · 2025Article
- Mirabegron treatment reduces myofibroblasts and CXCR2 expression in adipose tissue in obesity.Molecular medicine (Cambridge, Mass.) · 2025Article
- Evaluation of CNPase and TGFβ1/Smad Signalling Pathway Molecule Expression in Sinus Epithelial Tissues of Patients with Chronic Rhinosinusitis with (CRSwNP) and without Nasal Polyps (CRSsNP).Journal of personalized medicine · 2024Article
- Targeting cAMP signaling and phosphodiesterase 4 for liver disease treatment.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2024Article
- Cellular metabolism of substance P produces neurokinin-1 receptor peptide agonists with diminished cyclic AMP signaling.American journal of physiology. Cell physiology · 2024Article
- A network pharmacological study to unveil the mechanisms of xianlinggubao capsule in the treatment of osteoarthritis and osteoporosis.Archives of medical science : AMS · 2024Article
- A phosphodiesterase-4 inhibitor reduces lung inflammation and fibrosis in a hamster model of SARS-CoV-2 infection.Frontiers in immunology · 2023Article
- Loss-of-function variants in the schizophrenia risk gene SETD1A alter neuronal network activity in human neurons through the cAMP/PKA pathway.Cell reports · 2022Article
- Emerging Role of CREB in Epithelial to Mesenchymal Plasticity of Pancreatic Cancer.Frontiers in oncology · 2022Review
- Targeting GPCRs to treat cardiac fibrosis.Frontiers in cardiovascular medicine · 2022Review
- Impaired Wound Healing, Fibrosis, and Cancer: The Paradigm of Recessive Dystrophic Epidermolysis Bullosa.International journal of molecular sciences · 2021Review
- A Novel, Pan-PDE Inhibitor Exerts Anti-Fibrotic Effects in Human Lung Fibroblasts via Inhibition of TGF-β Signaling and Activation of cAMP/PKA Signaling.International journal of molecular sciences · 2020Article
- Platelet-derived factors impair placental chorionic gonadotropin beta-subunit synthesis.Journal of molecular medicine (Berlin, Germany) · 2020Article
- Preservation of circadian rhythms by the protein folding chaperone, BiP.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
cAMP is a key messenger of many hormones and neuropeptides, some of which modulate the composition of extracellular matrix. Treatment of human dermal fibroblasts with dibutyryl cyclic AMP and forskolin antagonized the inductive effects of transforming growth factor-beta (TGF-beta) on the expression of collagen, connective tissue growth factor, tissue inhibitor of matrix metalloproteinase-1, and plasminogen activator inhibitor type I, four prototypical TGF-beta-responsive genes. Increased intracellular cAMP prevented TGF-beta-induced Smad-specific gene transactivation, although TGF-beta-mediated Smad phosphorylation and nuclear translocation remained unaffected. However, increased cAMP levels abolished TGF-beta-induced interaction of Smad3 with its transcriptional co-activator cAMP-response element-binding protein (CREB)-binding protein (CBP)/p300. Overexpression of the transcriptional co-activator CBP/p300 rescued Smad-specific gene transcription in the presence of cAMP suggesting that sequestration of limited amounts of CBP/p300 by the activated cAMP/CREB pathway is the molecular basis of this inhibitory effect. These findings were extended by two functional assays. Increased intracellular cAMP levels suppressed the inductive activity of TGF-beta to contract mechanically unloaded collagen lattices and resulted in an attenuation of fibroblast migration of mechanically induced cell layer wounds. Of note, cAMP and TGF-beta synergistically induced hyaluronan synthase 2 (HAS2) expression and hyaluronan secretion, presumably via putative CREB-binding sites adjacent to Smad-binding sites within the HAS2 promoter. Our findings identify the cAMP pathway as a potent but differential and promoter-specific regulator of TGF-beta-mediated effects involved in extracellular matrix homeostasis.
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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.