ArticlePharmaceuticals (Basel, Switzerland)2023
GRK2 Mediates Macrophage Polarization by Regulating EP4-cAMP-pCREB Signaling in Ulcerative Colitis and the Therapeutic Effect of Paroxetine on Mice with DSS-Induced Colitis.
Article in Pharmaceuticals (Basel, Switzerland), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 12 citations in OpenAlex.
- Efficacy of Paroxetine as an Adjuvant Therapy in Rheumatoid Arthritis Patients: A Randomized Controlled Study.Drug design, development and therapy · 2025Trial
- The update of prostaglandin E2 receptor subtype 4 (EP4) in inflammatory diseases.Genes & diseases · 2026Review
- Beyond β-Adrenergic Receptor Brake: Compartment-Selective GRK2 Programs from Heart Failure to Cardio-Oncology.Kinases and phosphatases · 2026Article
- Repurposing Selective Serotonin Reuptake Inhibitors as Immunomodulators: Effects on Macrophage Activation and Polarization.Molecular neurobiology · 2026Review
- Ulcerative colitis: signaling pathways, therapeutic targets and interventional strategies.Signal transduction and targeted therapy · 2026Review
- Development and functional adaptation of intestinal macrophages across the lifespan.Clinical & translational immunology · 2026Review
- The intersection of GRK2 and PGE2 in rheumatoid arthritis: a comprehensive update on pathophysiology and treatment.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- From gut inflammation to psychiatric comorbidity: mechanisms and therapies for anxiety and depression in inflammatory bowel disease.Journal of neuroinflammation · 2025Review
- Integrated Microbiome and Metabolomic to Explore the Mechanism of Coptisine in Alleviating Ulcerative Colitis.Phytotherapy research : PTR · 2025Article
- Coptisine ameliorates colitis in mice by modulating cPLA2/TRPM8/CGRP-1 signaling pathways and strengthening intestinal barrier function.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2025Article
- Unveiling the Role of GRK2: From Immune Regulation to Cancer Therapeutics.Mediators of inflammation · 2025Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
G protein-coupled receptor kinase 2 (GRK2) is one of the cytosolic enzymes, and GRK2 translocation induces prostaglandin E2 receptor 4 (EP4) over-desensitization and reduces the level of cyclic adenosine monophosphate (cAMP) to regulate macrophage polarization. However, the role of GRK2 in the pathophysiology of ulcerative colitis (UC) remains unclear. In this study, we investigated the role of GRK2 in macrophage polarization in UC, using biopsies from patients, a GRK2 heterozygous mouse model with dextran sulfate sodium (DSS)-induced colitis, and THP-1 cells. The results showed that a high level of prostaglandin E2 (PGE2) stimulated the receptor EP4 and enhanced the transmembrane activity of GRK2 in colonic lamina propria mononuclear cells (LPMCs), resulting in a down-regulation of membrane EP4 expression. Then, the suppression of cAMP-cyclic AMP responsive element-binding (CREB) signal inhibited M2 polarization in UC. Paroxetine is acknowledged as one of the selective serotonin reuptake inhibitors (SSRI), which is also considered as a potent GRK2 inhibitor with a high selectivity for GRK2. We found that paroxetine could alleviate symptoms of DSS-induced colitis in mice by regulating GPCR signaling to affect macrophage polarization. Taken together, the current results show that GRK2 may act as a novel therapeutic target in UC by regulating macrophage polarization, and paroxetine as a GRK2 inhibitor may have therapeutic effect on mice with DSS-induced colitis.
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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.