ArticleInternational journal of molecular sciences2020
β2-Adrenergic Receptors Increase Cardiac Fibroblast Proliferation Through the Gαs/ERK1/2-Dependent Secretion of Interleukin-6.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 40 citations in OpenAlex.
- Biased signaling of β2-adrenergic receptor in physiological and pathological states.Cellular & molecular biology letters · 2026Review
- Kidney-Targeted Nanoparticle Delivery of Formoterol Mitigates Diabetic Kidney Disease without Adverse Cardiac Effects.ACS pharmacology & translational science · 2026Article
- A chitosan-based thermosensitive hydrogel incorporating propranolol nanoparticles to promote early osseointegration and peri-implant soft-tissue healing.RSC advances · 2026Article
- Cardioprotective Role of Captopril: From Basic to Applied Investigations.International journal of molecular sciences · 2025Review
- Decoding the regulatory roles of circular RNAs in cardiac fibrosis.Non-coding RNA research · 2025Review
- Isoproterenol mechanisms in inducing myocardial fibrosis and its application as an experimental model for the evaluation of therapeutic potential of phytochemicals and pharmaceuticals.Animal models and experimental medicine · 2025Review
- Cardiac autoantibodies promote a fibrotic transcriptome and reduced ventricular recovery in human myocarditis.Frontiers in immunology · 2025Article
- Esmolol improves sepsis outcomes through cardiovascular and immune modulation.Frontiers in pharmacology · 2025Article
- Review
- Hypoxic-Normoxic Crosstalk Activates Pro-Inflammatory Signaling in Human Cardiac Fibroblasts and Myocytes in a Post-Infarct Myocardium on a Chip.Advanced healthcare materials · 2024Article
- Cardiovascular Disease and miRNAs: Possible Oxidative Stress-Regulating Roles of miRNAs.Antioxidants (Basel, Switzerland) · 2024Review
- Modeling acute myocardial infarction and cardiac fibrosis using human induced pluripotent stem cell-derived multi-cellular heart organoids.Cell death & disease · 2024Article
- Isoproterenol induces MD2 activation by β-AR-cAMP-PKA-ROS signalling axis in cardiomyocytes and macrophages drives inflammatory heart failure.Acta pharmacologica Sinica · 2024Article
- β-blockers and metabolic modulation: unraveling the complex interplay with glucose metabolism, inflammation and oxidative stress.Frontiers in pharmacology · 2024Review
- [Smeglutide inhibits high glucose-induced proliferation of myocardial fibroblasts by downregulating TGFβ/Smad3 signaling].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- Post-myocardial infarction fibrosis: Pathophysiology, examination, and intervention.Frontiers in pharmacology · 2023Review
- Sex/Gender- and Age-Related Differences in β-Adrenergic Receptor Signaling in Cardiovascular Diseases.Journal of clinical medicine · 2022Review
- G Protein-Coupled Receptor and Their Kinases in Cell Biology and Disease.International journal of molecular sciences · 2022Article
- lncRNA Vgll3 Regulates the Activated Proliferation of Mouse Myocardial Fibroblasts through TGF-BioMed research international · 2022Article
- Immune cell βAmerican journal of physiology. Heart and circulatory physiology · 2021Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Fibroblasts are an important resident cell population in the heart involved in maintaining homeostasis and structure during normal conditions. They are also crucial in disease states for sensing signals and initiating the appropriate repair responses to maintain the structural integrity of the heart. This sentinel role of cardiac fibroblasts occurs, in part, through their ability to secrete cytokines. β-adrenergic receptors (βAR) are also critical regulators of cardiac function in the normal and diseased state and a major therapeutic target clinically. βAR are known to influence cytokine secretion in various cell types and they have been shown to be involved in cytokine production in the heart, but their role in regulating cytokine production in cardiac fibroblasts is not well understood. Thus, we hypothesized that βAR activation on cardiac fibroblasts modulates cytokine production to influence fibroblast function. Using primary fibroblast cultures from neonatal rats and adult mice, increased interleukin (IL)-6 expression and secretion occurred following β2AR activation. The use of pharmacological inhibitors and genetic manipulations showed that IL-6 elevations occurred through the Gαs-mediated activation of ERK1/2 and resulted in increased fibroblast proliferation. In vivo, a lack of β2AR resulted in increased infarct size following myocardial infarction and impaired wound closure in a murine dermal wound healing assay. These findings identify an important role for β2AR in regulating fibroblast proliferation through Gαs/ERK1/2-dependent alterations in IL-6 and may lead to the development of improved heart failure therapies through targeting fibrotic function of β2AR.
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