ArticleThe Journal of pharmacology and experimental therapeutics2013
Rolipram attenuates bile duct ligation-induced liver injury in rats: a potential pathogenic role of PDE4.
Article in The Journal of pharmacology and experimental therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- Misoprostol modulates cytokine expression through a cAMP pathway: Potential therapeutic implication for liver disease.Clinical immunology (Orlando, Fla.) · 2015Trial
- Pharmacokinetics and Biodistribution of Polymeric Nanoparticles Loaded with a Small Molecule Drug in Mice with Alcoholic Liver Disease.Molecular pharmaceutics · 2025Article
- ATP8B1 Deficiency Causes Phosphodiesterase 4-Mediated Glucagon Resistance and Impaired Gluconeogenesis in Mouse and Human Liver.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Targeting Phosphodiesterase 4 in Gastrointestinal and Liver Diseases: From Isoform-Specific Mechanisms to Precision Therapeutics.Biomedicines · 2025Review
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Depressive symptom as a risk factor for cirrhosis in patients with primary biliary cholangitis: Analysis based on Lasso-logistic regression and decision tree models.Brain and behavior · 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
- Therapeutic perspectives on PDE4B inhibition in adipose tissue dysfunction and chronic liver injury.Expert opinion on therapeutic targets · 2024Review
- Increased expression of phosphodiesterase 4 in activated hepatic stellate cells promotes cytoskeleton remodeling and cell migration.The Journal of pathology · 2023Article
- Dysregulated Cyclic Nucleotide Metabolism in Alcohol-Associated Steatohepatitis: Implications for Novel Targeted Therapies.Biology · 2023Article
- The Complexity and Multiplicity of the Specific cAMP Phosphodiesterase Family: PDE4, Open New Adapted Therapeutic Approaches.International journal of molecular sciences · 2022Review
- BI 1015550 is a PDE4B Inhibitor and a Clinical Drug Candidate for the Oral Treatment of Idiopathic Pulmonary Fibrosis.Frontiers in pharmacology · 2022Article
- Novel Liposomal Rolipram Formulation for Clinical Application to Reduce Emesis.Drug design, development and therapy · 2022Article
- Phosphodiesterase 4D Depletion/Inhibition Exerts Anti-Oncogenic Properties in Hepatocellular Carcinoma.Cancers · 2021Article
- cAMP Signaling in Pathobiology of Alcohol Associated Liver Disease.Biomolecules · 2020Review
- Phosphodiesterase 4 Inhibition as a Therapeutic Target for Alcoholic Liver Disease: From Bedside to Bench.Hepatology (Baltimore, Md.) · 2019Article
- Role of cAMP and phosphodiesterase signaling in liver health and disease.Cellular signalling · 2018Review
- Paper-based inkjet bioprinting to detect fluorescence resonance energy transfer for the assessment of anti-inflammatory activity.Scientific reports · 2018Article
- Roflumilast reverses polymicrobial sepsis-induced liver damage by inhibiting inflammation in mice.Laboratory investigation; a journal of technical methods and pathology · 2017Article
- Medical Management of Severe Alcoholic Hepatitis: Expert Review from the Clinical Practice Updates Committee of the AGA Institute.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2017Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Anti-inflammatory and antifibrotic effects of the broad spectrum phosphodiesterase (PDE) inhibitor pentoxifylline have suggested an important role for cyclic nucleotides in the pathogenesis of hepatic fibrosis; however, studies examining the role of specific PDEs are lacking. Endotoxemia and Toll-like receptor 4 (TLR4)-mediated inflammatory and profibrotic signaling play a major role in the development of hepatic fibrosis. Because cAMP-specific PDE4 critically regulates lipopolysaccharide (LPS)-TLR4-induced inflammatory cytokine expression, its pathogenic role in bile duct ligation-induced hepatic injury and fibrogenesis in Sprague-Dawley rats was examined. Initiation of cholestatic liver injury and fibrosis was accompanied by a significant induction of PDE4A, B, and D expression and activity. Treatment with the PDE4-specific inhibitor rolipram significantly decreased liver PDE4 activity, hepatic inflammatory and profibrotic cytokine expression, injury, and fibrosis. At the cellular level, in relevance to endotoxemia and inflammatory cytokine production, PDE4B was observed to play a major regulatory role in the LPS-inducible tumor necrosis factor (TNF) production by isolated Kupffer cells. Moreover, PDE4 expression was also involved in the in vitro activation and transdifferentiation of isolated hepatic stellate cells (HSCs). Particularly, PDE4A, B, and D upregulation preceded induction of the HSC activation marker α-smooth muscle actin (α-SMA). In vitro treatment of HSCs with rolipram effectively attenuated α-SMA, collagen expression, and accompanying morphologic changes. Overall, these data strongly suggest that upregulation of PDE4 expression during cholestatic liver injury plays a potential pathogenic role in the development of inflammation, injury, and 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.