ArticleInternational journal of molecular sciences2022
Regulator of G-Protein Signaling-4 Attenuates Cardiac Adverse Remodeling and Neuronal Norepinephrine Release-Promoting Free Fatty Acid Receptor FFAR3 Signaling.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- The Gut Microbiota-Metabolite-Host Axis in Cardiometabolic Diseases: Bridging Bench to Bedside.Cardiovascular drugs and therapy · 2026Review
- Gut‑bone metabolites: SCFAs, polyamines and microbial metabolomics in osteoporosis risk and therapy (Review).International journal of molecular medicine · 2026Review
- Baicalein mitigates epithelial barrier impairment and microbiota dysbiosis in allergic asthmatic mice via the gut‑lung axis.Chinese medicine · 2026Article
- Dietary β-hydroxy-β-methyl butyrate supplementation improves intestinal health and growth performance in Tibetan sheep lambs via modulating small intestinal microbiota.Journal of animal science and biotechnology · 2026Article
- Review
- Dapagliflozin enhances gut barrier function in rats with chronic myocardial infarction by modulating gut microbiota balance.Annals of translational medicine · 2025Article
- Unraveling the Translational Relevance of β-Hydroxybutyrate as an Intermediate Metabolite and Signaling Molecule.International journal of molecular sciences · 2025Review
- The Gut-Heart Axis: Molecular Perspectives and Implications for Myocardial Infarction.International journal of molecular sciences · 2024Review
- Endocrine-Disruptive Effects of Adenylate Cyclase Activator Forskolin: In Vitro and In Vivo Evidence.Toxics · 2024Article
- Article
- Gut microbiota metabolism disturbance is associated with postoperative atrial fibrillation after coronary artery bypass grafting.NPJ cardiovascular health · 2024Article
- Gut-Derived Short-Chain Fatty Acids and Macrophage Modulation: Exploring Therapeutic Potentials in Pulmonary Fungal Infections.Clinical reviews in allergy & immunology · 2024Review
- Differential Modulation of Catecholamine and Adipokine Secretion by the Short Chain Fatty Acid Receptor FFAR3 and αInternational journal of molecular sciences · 2024Article
- GLP-1 receptor agonists and myocardial metabolism in atrial fibrillation.Journal of pharmaceutical analysis · 2024Review
- Aldehyde Dehydrogenase 2 (ALDH2) Deficiency, Obesity, and Atrial Fibrillation Susceptibility: Unraveling the Connection.International journal of molecular sciences · 2024Article
- Modified Zuo Gui Wan Ameliorates Ovariectomy-Induced Osteoporosis in Rats by Regulating the SCFA-GPR41-p38MAPK Signaling Pathway.Drug design, development and therapy · 2024Article
- Nicotine Diminishes Alpha2-Adrenergic Receptor-Dependent Protection Against Oxidative Stress in H9c2 Cardiomyocytes.Drug design, development and therapy · 2024Article
- Gut microbiota alterations in acute myocardial infarction: (diabetic) context is everything.Annals of translational medicine · 2023Article
- Editorial for theInternational journal of molecular sciences · 2023Article
- JNK Cascade-Induced Apoptosis-A Unique Role in GqPCR Signaling.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Propionic acid is a cell nutrient but also a stimulus for cellular signaling. Free fatty acid receptor (FFAR)-3, also known as GPR41, is a Gi/o protein-coupled receptor (GPCR) that mediates some of the propionate's actions in cells, such as inflammation, fibrosis, and increased firing/norepinephrine release from peripheral sympathetic neurons. The regulator of G-protein Signaling (RGS)-4 inactivates (terminates) both Gi/o- and Gq-protein signaling and, in the heart, protects against atrial fibrillation via calcium signaling attenuation. RGS4 activity is stimulated by β-adrenergic receptors (ARs) via protein kinase A (PKA)-dependent phosphorylation. Herein, we examined whether RGS4 modulates cardiac FFAR3 signaling/function. We report that RGS4 is essential for dampening of FFAR3 signaling in H9c2 cardiomyocytes, since siRNA-mediated RGS4 depletion significantly enhanced propionate-dependent cAMP lowering, Gi/o activation, p38 MAPK activation, pro-inflammatory interleukin (IL)-1β and IL-6 production, and pro-fibrotic transforming growth factor (TGF)-β synthesis. Additionally, catecholamine pretreatment blocked propionic acid/FFAR3 signaling via PKA-dependent activation of RGS4 in H9c2 cardiomyocytes. Finally, RGS4 opposes FFAR3-dependent norepinephrine release from sympathetic-like neurons (differentiated Neuro-2a cells) co-cultured with H9c2 cardiomyocytes, thereby preserving the functional βAR number of the cardiomyocytes. In conclusion, RGS4 appears essential for propionate/FFAR3 signaling attenuation in both cardiomyocytes and sympathetic neurons, leading to cardioprotection against inflammation/adverse remodeling and to sympatholysis, respectively.
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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.