ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2012
Defining the cellular repertoire of GPCRs identifies a profibrotic role for the most highly expressed receptor, protease-activated receptor 1, in cardiac fibroblasts.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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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
44 citing papers in PubMed, 70 citations in OpenAlex.
- Histamine H1 receptor: A target to treat pancreatic ductal adenocarcinoma (PDAC) by repurposing approved H1-antihistamines?Cell signaling · 2026Article
- Targeting cardiac fibrosis with Chimeric Antigen Receptor-Engineered Cells.Molecular and cellular biochemistry · 2025Review
- Gastrodin attenuates diabetic cardiomyopathy characterized by myocardial fibrosis by inhibiting the KLK8-PAR1 signaling axis.Chinese medicine · 2024Article
- Direct interrogation of context-dependent GPCR activity with a universal biosensor platform.Cell · 2024Article
- Direct interrogation of context-dependent GPCR activity with a universal biosensor platform.bioRxiv : the preprint server for biology · 2024Article
- Suppression of Heart Failure With PAR1 Pepducin Technology in a Pressure Overload Model in Mice.Circulation. Heart failure · 2023Article
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- Targeting GPCRs to treat cardiac fibrosis.Frontiers in cardiovascular medicine · 2022Review
- Article
- Rivaroxaban attenuates cardiac hypertrophy by inhibiting protease-activated receptor-2 signaling in renin-overexpressing hypertensive mice.Hypertension research : official journal of the Japanese Society of Hypertension · 2021Article
- GRK5 is a regulator of fibroblast activation and cardiac fibrosis.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Myofibroblasts and Fibrosis: Mitochondrial and Metabolic Control of Cellular Differentiation.Circulation research · 2020Review
- Targeting GPCR Signaling for Idiopathic Pulmonary Fibrosis Therapies.Trends in pharmacological sciences · 2020Review
- Syndecan-4 Protects the Heart From the Profibrotic Effects of Thrombin-Cleaved Osteopontin.Journal of the American Heart Association · 2020Article
- Angiotensin-II-Evoked CaCells · 2020Article
- Thrombin receptor PAR4 drives canonical NLRP3 inflammasome signaling in the heart.Basic research in cardiology · 2020Article
- Cardiac Expression of Factor X Mediates Cardiac Hypertrophy and Fibrosis in Pressure Overload.JACC. Basic to translational science · 2020Article
- GPCRs show widespread differential mRNA expression and frequent mutation and copy number variation in solid tumors.PLoS biology · 2019Article
- Detection and Quantification of GPCR mRNA: An Assessment and Implications of Data from High-Content Methods.ACS omega · 2019Article
- CaJournal of cardiovascular development and disease · 2019Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
G-protein-coupled receptors (GPCRs) have many roles in cell regulation and are commonly used as drug targets, but the repertoire of GPCRs expressed by individual cell types has not been defined. Here we use an unbiased approach, GPCR RT-PCR array, to define the expression of nonchemosensory GPCRs by cardiac fibroblasts (CFs) isolated from Rattus norvegicus. CFs were selected because of their importance for cardiac structure and function and their contribution to cardiac fibrosis, which occurs with advanced age, after acute injury (e.g., myocardial infarction), and in disease states (e.g., diabetes mellitus, hypertension). We discovered that adult rat CFs express 190 GPCRs and that activation of protease-activated receptor 1 (PAR1), the most highly expressed receptor, raises the expression of profibrotic markers in rat CFs, resulting in a 60% increase in collagen synthesis and conversion to a profibrogenic myofibroblast phenotype. We use siRNA knockdown of PAR1 (90% decrease in mRNA) to show that the profibrotic effects of thrombin are PAR1-dependent. These findings, which define the expression of GPCRs in CFs, provide a proof of principle of an approach to discover previously unappreciated, functionally relevant GPCRs and reveal a potential role for thrombin and PAR1 in wound repair and pathophysiology of the adult heart.
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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.