ArticleMolecular biology of the cell2009
Expression and activity of phosphodiesterase isoforms during epithelial mesenchymal transition: the role of phosphodiesterase 4.
Article in Molecular biology of the cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 48 papers.
What it found
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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.
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Who cites it
48 citing papers in PubMed, 98 citations in OpenAlex.
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- Hyperglycaemia-Induced Metabolic Stress Promotes EMT-Driven Therapeutic Resistance in Cancer: Evidence of a Deleterious Feed-Forward Cycle.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Pan-Cancer Analysis of Cyclic Nucleotide Phosphodiesterases (PDEs) Expression, Variation, and Prognostic Significance.ACS omega · 2025Article
- PDE4-Selective Inhibition in Chronic Obstructive Pulmonary Disease and Pulmonary Fibrosis: Different Agents or Different Targets?Life (Basel, Switzerland) · 2025Review
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- PDE10A as a novel diagnostic and therapeutic target in cancer: insights and challenges.Frontiers in oncology · 2025Review
- Novel Factors Regulating Proliferation, Migration, and Differentiation of Fibroblasts, Keratinocytes, and Vascular Smooth Muscle Cells during Wound Healing.Biomedicines · 2024Review
- An Endosomal Acid-Regulatory Feedback System Rewires Cytosolic cAMP Metabolism and Drives Tumor Progression.Molecular cancer research : MCR · 2024Article
- Pan-Phosphodiesterase Inhibitors Attenuate TGF-β-Induced Pro-Fibrotic Phenotype in Alveolar Epithelial Type II Cells by Downregulating Smad-2 Phosphorylation.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Global Gene Expression Regulation Mediated by TGFβ Through H3K9me3 Mark.Cancer informatics · 2022Article
- The regulatory role of PDE4B in the progression of inflammatory function study.Frontiers in pharmacology · 2022Review
- BI 1015550 is a PDE4B Inhibitor and a Clinical Drug Candidate for the Oral Treatment of Idiopathic Pulmonary Fibrosis.Frontiers in pharmacology · 2022Article
- Article
- Constructing gene regulatory networks using epigenetic data.NPJ systems biology and applications · 2021Article
- Phosphodiesterase 4 mediates interleukin-8-induced heterologous desensitization of the βFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- TGF‑β1: Gentlemanly orchestrator in idiopathic pulmonary fibrosis (Review).International journal of molecular medicine · 2021Review
- Arecoline Enhances Phosphodiesterase 4A Activity to Promote Transforming Growth Factor-β-Induced Buccal Mucosal Fibroblast Activation via cAMP-Epac1 Signaling Pathway.Frontiers in pharmacology · 2021Article
- MicroRNA-133 TargetsJournal of Cancer · 2021Article
- Article
- PDE4 subtypes in cancer.Oncogene · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epithelial-mesenchymal transition (EMT) has emerged as a critical event in the pathogenesis of organ fibrosis and cancer and is typically induced by the multifunctional cytokine transforming growth factor (TGF)-beta1. The present study was undertaken to evaluate the potential role of phosphodiesterases (PDEs) in TGF-beta1-induced EMT in the human alveolar epithelial type II cell line A549. Stimulation of A549 with TGF-beta1 induced EMT by morphological alterations and by expression changes of the epithelial phenotype markers E-cadherin, cytokeratin-18, zona occludens-1, and the mesenchymal phenotype markers, collagen I, fibronectin, and alpha-smooth muscle actin. Interestingly, TGF-beta1 stimulation caused twofold increase in total cAMP-PDE activity, contributed mostly by PDE4. Furthermore, mRNA and protein expression demonstrated up-regulation of PDE4A and PDE4D isoforms in TGF-beta1-stimulated cells. Most importantly, treatment of TGF-beta1 stimulated epithelial cells with the PDE4-selective inhibitor rolipram or PDE4 small interfering RNA potently inhibited EMT changes in a Smad-independent manner by decreasing reactive oxygen species, p38, and extracellular signal-regulated kinase phosphorylation. In contrast, the ectopic overexpression of PDE4A and/or PDE4D resulted in a significant loss of epithelial marker E-cadherin but did not result in changes of mesenchymal markers. In addition, Rho kinase signaling activated by TGF-beta1 during EMT demonstrated to be a positive regulator of PDE4. Collectively, the findings presented herein suggest that TGF-beta1 mediated up-regulation of PDE4 promotes EMT in alveolar epithelial cells. Thus, targeting PDE4 isoforms may be a novel approach to attenuate EMT-associated lung diseases such as pulmonary fibrosis and lung cancer.
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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.