ArticleThe Journal of clinical investigation2008
Multidrug resistance-associated protein 4 regulates cAMP-dependent signaling pathways and controls human and rat SMC proliferation.
Article in The Journal of clinical investigation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
47 citing papers in PubMed, 119 citations in OpenAlex.
- Extracellular-cAMP suppresses pulmonary arterial hypertension-induced ventricular arrhythmias.Journal of molecular and cellular cardiology · 2026Article
- Insights and perspectives into the etiology of TKI-induced cardiotoxicity.ASPET discovery · 2026Article
- Protein Kinase A and assembly of an ABCC4 protein network.Nature communications · 2025Article
- Review
- Review on Bortezomib Resistance in Multiple Myeloma and Potential Role of Emerging Technologies.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Specific inhibition of the transporter MRP4/ABCC4 affects multiple signaling pathways and thrombus formation in human platelets.Haematologica · 2022Article
- Multidrug-resistant protein inhibitor and phosphodiesterase inhibitor potentiate the vasodilator effect induced by photobiomodulation in isolated aortic rings.Lasers in medical science · 2022Article
- Augustine Blood Group System and Equilibrative Nucleoside Transporter 1.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2022Review
- PDE-Mediated Cyclic Nucleotide Compartmentation in Vascular Smooth Muscle Cells: From Basic to a Clinical Perspective.Journal of cardiovascular development and disease · 2021Review
- MRP4 over-expression has a role on both reducing nitric oxide-dependent antiplatelet effect and enhancing ADP induced platelet activation.Journal of thrombosis and thrombolysis · 2021Article
- Changes in Gene Expression Profiling and Phenotype in Aged Multidrug Resistance Protein 4-Deficient Mouse Retinas.Antioxidants (Basel, Switzerland) · 2021Article
- Genetics of blood malignancies among Iranian population: an overview.Diagnostic pathology · 2020Review
- Insights into exchange factor directly activated by cAMP (EPAC) as potential target for cancer treatment.Molecular and cellular biochemistry · 2018Review
- A Predictive 7-Gene Assay and Prognostic Protein Biomarkers for Non-small Cell Lung Cancer.EBioMedicine · 2018Article
- Platelet Transcriptome Profiling in HIV and ATP-Binding Cassette Subfamily C Member 4 (ABCC4) as a Mediator of Platelet Activity.JACC. Basic to translational science · 2018Article
- ABC Transport Proteins in Cardiovascular Disease-A Brief Summary.Molecules (Basel, Switzerland) · 2017Review
- R-Flurbiprofen Traps Prostaglandins within Cells by Inhibition of Multidrug Resistance-Associated Protein-4.International journal of molecular sciences · 2016Article
- Genome-wide rare copy number variation screening in ulcerative colitis identifies potential susceptibility loci.BMC medical genetics · 2016Article
- Differential Proteomics Analysis of Colonic Tissues in Patients of Slow Transit Constipation.BioMed research international · 2016Article
- Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The second messengers cAMP and cGMP can be degraded by specific members of the phosphodiesterase superfamily or by active efflux transporters, namely the multidrug resistance-associated proteins (MRPs) MRP4 and MRP5. To determine the role of MRP4 and MRP5 in cell signaling, we studied arterial SMCs, in which the effects of cyclic nucleotide levels on SMC proliferation have been well established. We found that MRP4, but not MRP5, was upregulated during proliferation of isolated human coronary artery SMCs and following injury of rat carotid arteries in vivo. MRP4 inhibition significantly increased intracellular cAMP and cGMP levels and was sufficient to block proliferation and to prevent neointimal growth in injured rat carotid arteries. The antiproliferative effect of MRP4 inhibition was related to PKA/CREB pathway activation. Here we provide what we believe to be the first evidence that MRP4 acts as an independent endogenous regulator of intracellular cyclic nucleotide levels and as a mediator of cAMP-dependent signal transduction to the nucleus. We also identify MRP4 inhibition as a potentially new way of preventing abnormal VSMC proliferation.
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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.