ArticlePloS one2015
Functional interaction between angiotensin II receptor type 1 and chemokine (C-C motif) receptor 2 with implications for chronic kidney disease.
Article in PloS one, 2015. 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.
- Combination of the chemokine receptor type 2 (CCR2) antagonist DMX-200 and candesartan for COVID-19: a randomised controlled trial.BMJ open · 2024Trial
- GPCR Heterodimers: Implications for Biased Signaling.Handbook of experimental pharmacology · 2026Review
- DMX-200 in Patients With Primary Focal Segmental Glomerulosclerosis: Results of the Phase 2 ACTION2 Trial.Kidney international reports · 2025Article
- Investigation of Strategies to Block Downstream Effectors of AT1R-Mediated Signalling to Prevent Aneurysm Formation in Marfan Syndrome.International journal of molecular sciences · 2024Article
- CXCL17 is an allosteric inhibitor of CXCR4 through a mechanism of action involving glycosaminoglycans.Science signaling · 2024Article
- Immunomodulation and immunopharmacology in heart failure.Nature reviews. Cardiology · 2024Review
- The chemokine receptor CCR8 is not a high-affinity receptor for the human chemokine CCL18.PloS one · 2024Article
- GPCR heteromers: An overview of their classification, function and physiological relevance.Frontiers in endocrinology · 2022Review
- Novel Pharmacology Following Heteromerization of the Angiotensin II Type 2 Receptor and the Bradykinin Type 2 Receptor.Frontiers in endocrinology · 2022Article
- Profiling novel pharmacology of receptor complexes using Receptor-HIT.Biochemical Society transactions · 2021Review
- Systematic Assessment of Chemokine Signaling at Chemokine Receptors CCR4, CCR7 and CCR10.International journal of molecular sciences · 2021Article
- Investigation of Receptor Heteromers Using NanoBRET Ligand Binding.International journal of molecular sciences · 2021Article
- SARS-CoV-2 Infection and Cardioncology: From Cardiometabolic Risk Factors to Outcomes in Cancer Patients.Cancers · 2020Review
- Angiotensin Receptors Heterodimerization and Trafficking: How Much Do They Influence Their Biological Function?Frontiers in pharmacology · 2020Review
- Interplay Between Angiotensin II Type 1 Receptor and Thrombin Receptor Revealed by Bioluminescence Resonance Energy Transfer Assay.Frontiers in pharmacology · 2020Article
- Influence of Chemokine N-Terminal Modification on Biased Agonism at the Chemokine Receptor CCR1.International journal of molecular sciences · 2019Article
- Evaluation and extension of the two-site, two-step model for binding and activation of the chemokine receptor CCR1.The Journal of biological chemistry · 2019Article
- The Role of β-Arrestin Proteins in Organization of Signaling and Regulation of the AT1 Angiotensin Receptor.Frontiers in endocrinology · 2019Review
- Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology.Physiological reviews · 2018Review
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Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Understanding functional interactions between G protein-coupled receptors is of great physiological and pathophysiological importance. Heteromerization provides one important potential mechanism for such interaction between different signalling pathways via macromolecular complex formation. Previous studies suggested a functional interplay between angiotensin II receptor type 1 (AT1) and Chemokine (C-C motif) Receptor 2 (CCR2). However the molecular mechanisms are not understood. We investigated AT1-CCR2 functional interaction in vitro using bioluminescence resonance energy transfer in HEK293 cells and in vivo using subtotal-nephrectomized rats as a well-established model for chronic kidney disease. Our data revealed functional heteromers of these receptors resulting in CCR2-Gαi1 coupling being sensitive to AT1 activation, as well as apparent enhanced β-arrestin2 recruitment with agonist co-stimulation that is synergistically reversed by combined antagonist treatment. Moreover, we present in vivo findings where combined treatment with AT1- and CCR2-selective inhibitors was synergistically beneficial in terms of decreasing proteinuria, reducing podocyte loss and preventing renal injury independent of blood pressure in the subtotal-nephrectomized rat model. Our findings further support a role for G protein-coupled receptor functional heteromerization in pathophysiology and provide insights into previous observations indicating the importance of AT1-CCR2 functional interaction in inflammation, renal and hypertensive disorders.
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