{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T14:57:53Z","timestamp":1783177073857,"version":"3.54.6"},"reference-count":152,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2021,3,21]],"date-time":"2021-03-21T00:00:00Z","timestamp":1616284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek Vlaanderen","doi-asserted-by":"crossref","award":["N\u00b0 1702419N"],"award-info":[{"award-number":["N\u00b0 1702419N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The apelinergic system (AS) is a novel pleiotropic system with an essential role in renal and cardiovascular physiology and disease, including water homeostasis and blood pressure regulation. It consists of two highly conserved peptide ligands, apelin and apela, and a G-protein-coupled apelin receptor. The two ligands have many isoforms and a short half-life and exert both similar and divergent effects. Vasopressin, apelin and their receptors colocalize in hypothalamic regions essential for body fluid homeostasis and interact at the central and renal levels to regulate water homeostasis and diuresis in inverse directions. In addition, the AS and renin\u2013angiotensin system interact both systemically and in the kidney, with implications for the cardiovascular system. A role for the AS in diverse pathological states, including disorders of sodium and water balance, hypertension, heart failure, pre-eclampsia, acute kidney injury, sepsis and diabetic nephropathy, has recently been reported. Furthermore, several metabolically stable apelin analogues have been developed, with potential applications in diverse diseases. We review here what is currently known about the physiological functions of the AS, focusing on renal, cardiovascular and metabolic homeostasis, and the role of the AS in associated diseases. We also describe several hurdles and research opportunities worthy of the attention of the nephrology community.<\/jats:p>","DOI":"10.1093\/ndt\/gfab070","type":"journal-article","created":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T20:10:49Z","timestamp":1616011849000},"page":"2314-2326","source":"Crossref","is-referenced-by-count":20,"title":["The emerging role of the apelinergic system in kidney physiology and disease"],"prefix":"10.1093","volume":"37","author":[{"given":"Peter","family":"Janssens","sequence":"first","affiliation":[{"name":"PKD Research Group, Laboratory of Pediatrics, Department of Development and Regeneration, KU Leuven , Leuven, Belgium"},{"name":"Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussell), Department of Nephrology, Laarbeeklaan 101, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Paul","family":"Decuypere","sequence":"additional","affiliation":[{"name":"PKD Research Group, Laboratory of Pediatrics, Department of Development and Regeneration, KU Leuven , Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bert","family":"Bammens","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Dialysis and Renal Transplantation, University Hospitals Leuven , Leuven, Belgium"},{"name":"Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven , Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Llorens-Cortes","sequence":"additional","affiliation":[{"name":"Laboratory of Central Neuropeptides in the Regulation of Body Fluid Homeostasis and Cardiovascular Functions, Center for Interdisciplinary Research in Biology, Coll\u00e8ge de France, INSERM U1050, CNRS UMR 7241 , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudi","family":"Vennekens","sequence":"additional","affiliation":[{"name":"Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, VIB-KU Leuven Center for Brain and Disease, KU Leuven , Leuven, Belgium and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Djalila","family":"Mekahli","sequence":"additional","affiliation":[{"name":"PKD Research Group, Laboratory of Pediatrics, Department of Development and Regeneration, KU Leuven , Leuven, Belgium"},{"name":"Department of Pediatric Nephrology and Organ Transplantation, University Hospitals Leuven , Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,3,21]]},"reference":[{"key":"2022112304492692000_gfab070-B1","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/0378-1119(93)90495-O","article-title":"A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11","volume":"136","author":"O'Dowd","year":"1993","journal-title":"Gene"},{"key":"2022112304492692000_gfab070-B2","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1006\/bbrc.1998.9489","article-title":"Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor","volume":"251","author":"Tatemoto","year":"1998","journal-title":"Biochem Biophys Res Commun"},{"key":"2022112304492692000_gfab070-B3","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/j.devcel.2013.11.002","article-title":"ELABELA: a hormone essential for heart development signals via the apelin receptor","volume":"27","author":"Chng","year":"2013","journal-title":"Dev Cell"},{"key":"2022112304492692000_gfab070-B4","doi-asserted-by":"crossref","first-page":"1248636","DOI":"10.1126\/science.1248636","article-title":"Toddler: an embryonic signal that promotes cell movement via apelin receptors","volume":"343","author":"Pauli","year":"2014","journal-title":"Science"},{"key":"2022112304492692000_gfab070-B5","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1002\/cphy.c170028","article-title":"Apelinergic system structure and function","volume":"8","author":"Shin","year":"2017","journal-title":"Compr Physiol"},{"key":"2022112304492692000_gfab070-B6","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1124\/pr.119.017533","article-title":"International union of basic and clinical pharmacology. 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Structure and pharmacology of the apelin receptor with a recommendation that Elabela\/Toddler is a second endogenous peptide ligand","volume":"71","author":"Read","year":"2019","journal-title":"Pharmacol Rev"},{"key":"2022112304492692000_gfab070-B7","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/s00726-018-2674-8","article-title":"Proapelin is processed extracellularly in a cell line-dependent manner with clear modulation by proprotein convertases","volume":"51","author":"Shin","year":"2019","journal-title":"Amino Acids"},{"key":"2022112304492692000_gfab070-B8","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.1002\/rcm.4718","article-title":"Liquid chromatography\/tandem mass spectrometry assay for the absolute quantification of the expected circulating apelin peptides in human plasma","volume":"24","author":"Mesmin","year":"2010","journal-title":"Rapid Commun Mass 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