ArticleThe Journal of biological chemistry2015
Apela Regulates Fluid Homeostasis by Binding to the APJ Receptor to Activate Gi Signaling.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 113 citations in OpenAlex.
- The chemokine receptor-like fourth extracellular loop of the apelin receptor differentially regulates apelin and elabela binding and signalling.British journal of pharmacology · 2026Article
- The Apelin-APJ Axis in Heart Failure: Mechanistic Insights, Clinical Evidence, and Translational Challenges.Cardiovascular drugs and therapy · 2026Review
- Elabela in Lipid-Related Cardiometabolic Dysfunction: A Critical Narrative Review.Metabolites · 2026Review
- ELABELA Targets Mitochondria to Modulate Heart Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- International Union of Basic and Clinical Pharmacology. CXXI. Apelin receptor pharmacology in the human cardiovascular system and emerging clinical applications.Pharmacological reviews · 2026Review
- ELABELA: A Potential Therapeutic Target for Ischemia-Reperfusion Injury.Biomolecules · 2026Review
- Review
- Role and therapeutic potential of elabela in renal disease: from molecular mechanisms to clinical applications.Endocrine connections · 2025Review
- ELABELA Ameliorates Atherosclerosis Through Restoring the M1/M2 Macrophage Balance inJournal of the American Heart Association · 2025Article
- Article
- Metabolically stable apelin analogs: development and functional role in water balance and cardiovascular function.Clinical science (London, England : 1979) · 2025Review
- Risk prediction of kidney function in long-term kidney transplant recipients.Frontiers in medicine · 2025Article
- Fc-Elabela mitigates heart failure without liver and renal toxicity in mice.Frontiers in pharmacology · 2025Article
- ELABELA-derived peptide ELA13 attenuates kidney fibrosis by inhibiting the Smad and ERK signaling pathways.Journal of Zhejiang University. Science. B · 2024Article
- Serum Elabela expression is decreased in hypertensive patients and could be associated with the progression of hypertensive renal damage.European journal of medical research · 2024Article
- The Apelin/APJ System: A Potential Therapeutic Target for Sepsis.Journal of inflammation research · 2024Review
- Targeting the apelin system for the treatment of cardiovascular diseases.Cardiovascular research · 2023Review
- Global genetic diversity, introgression, and evolutionary adaptation of indicine cattle revealed by whole genome sequencing.Nature communications · 2023Article
- Apelin is altered in subjects with autosomal dominant polycystic kidney disease and preserved kidney function.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2023Article
- Apelin Is a Prototype of Novel Drugs for the Treatment of Acute Myocardial Infarction and Adverse Myocardial Remodeling.Pharmaceutics · 2023Review
4 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Apela (APJ early endogenous ligand, also known as elabela or toddler) is a recently discovered peptide hormone. Based on genetic studies in zebrafish, apela was found to be important for endoderm differentiation and heart development during embryogenesis. Although common phenotypes of apela and APJ-null zebrafish during embryonic development suggested that apela interacts with the APJ receptor, kinetics of apela binding to APJ and intracellular signaling pathways for apela remain unknown. The role of apela in adults is also uncertain. Using a chimeric apela ligand, we showed direct binding of apela to APJ with high affinity (Kd = 0.51 nm) and the ability of apelin, the known peptide ligand for APJ, to compete for apela binding. Apela, similar to apelin, acts through the inhibitory G protein pathway by inhibiting forskolin-stimulated cAMP production and by inducing ERK1/2 phosphorylation. In adult rats, apela is expressed exclusively in the kidney, unlike the wide tissue distribution of apelin. In vivo studies demonstrated the ability of apela to regulate fluid homeostasis by increasing diuresis and water intake. Dose-response studies further indicated that apela induces 2- and 5-fold higher maximal responses than apelin in ERK1/2 phosphorylation and diuresis/water intake, respectively. After designing an apela antagonist, we further demonstrated the role of endogenous ligand(s) in regulating APJ-mediated fluid homeostasis. Our results identified apela as a potent peptide hormone capable of regulating fluid homeostasis in adult kidney through coupling to the APJ-mediated Gi signaling pathway.
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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.