{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T17:49:18Z","timestamp":1775065758491,"version":"3.50.1"},"posted":{"date-parts":[[2026,3,30]]},"group-title":"Pharmacology and Toxicology","reference-count":56,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/501100022885","name":"Polycystic Kidney Disease Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100022885","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIH\/NIDDK","award":["R01DK115727"],"award-info":[{"award-number":["R01DK115727"]}]},{"name":"NIH","award":["U54 DK126126"],"award-info":[{"award-number":["U54 DK126126"]}]},{"name":"NIH","award":["NIH S10OD036343"],"award-info":[{"award-number":["NIH S10OD036343"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disorder marked by numerous renal cysts that impair kidney function, with about half of affected individuals progressing to kidney failure by midlife. Patients exhibit reduced circulating apelin, a ligand of the apelin receptor, known to regulate cardiovascular function including hypertension. We tested whether diminished apelin signaling contributes to cystogenesis and if exogenous apelin receptor activation can improve disease outcomes.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    Plasma samples from age- and sex-matched healthy controls and ADPKD participants were analyzed for circulating apelin peptides. To assess direct cystic effects, primary ADPKD renal epithelial cells were grown as 3D collagen-embedded cysts and treated with apelin agonists. Male and female\n                    <jats:italic>\n                      Pkd1\n                      <jats:sup>RC\/RC<\/jats:sup>\n                      ; Pkd2\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    (PKD) mice were treated for 27 days with apelin agonists, vehicle, or the standard of care drug, Mozavaptan. Kidney and heart weight ratios, BUN, renal cAMP, and kidney transcriptional profiles were evaluated.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Circulating apelin peptides were significantly reduced in ADPKD patients despite normal kidney function (eGFR, BUN, and creatinine).\n                    <jats:italic>In vitro<\/jats:italic>\n                    , both apelin and the small molecule apelin receptor agonist Azelaprag inhibited cyst growth. Apelin and Mozavaptan reduced kidney weight, cystic index, blood urea nitrogen and renal cAMP in PKD mice, whereas Azelaprag did not. Apelin downregulated expression of genes associated with cyst progression, including\n                    <jats:italic>Lcn2 (Ngal)<\/jats:italic>\n                    ,\n                    <jats:italic>Postn,<\/jats:italic>\n                    and\n                    <jats:italic>Havcr1 (Kim-1)<\/jats:italic>\n                    . Mozavaptan, but not apelin, induced diuresis and reduced urinary concentration.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Apelin receptor activation by exogenous apelin inhibited cAMP synthesis and cyst growth and improved kidney function in an orthologous mouse model of ADPKD. We propose that the apelin receptor may be a potential therapeutic target in ADPKD.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.03.26.714294","type":"posted-content","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T18:00:14Z","timestamp":1774893614000},"source":"Crossref","is-referenced-by-count":0,"title":["Apelin inhibits cyst growth and improves kidney function in mice with polycystic kidney disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6212-9518","authenticated-orcid":false,"given":"Duuamene","family":"Nyimanu","sequence":"first","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Internal Medicine"},{"name":"Jared Grantham Kidney Institute"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anubhav","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Jared Grantham Kidney Institute"},{"name":"Department of Cell Biology and Physiology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen C","family":"Parnell","sequence":"additional","affiliation":[{"name":"Jared Grantham Kidney Institute"},{"name":"Department of Biochemistry and Molecular Biology University of Kansas Medical Center 3901 Rainbow Blvd. Kansas City, KS 66160 United States of America"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darren P","family":"Wallace","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Internal Medicine"},{"name":"Jared Grantham Kidney Institute"},{"name":"Department of Cell Biology and Physiology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan SL","family":"Yu","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Internal Medicine"},{"name":"Jared Grantham Kidney Institute"},{"name":"Department of Cell Biology and Physiology"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026040108501076000_2026.03.26.714294v1.1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00018.2024"},{"key":"2026040108501076000_2026.03.26.714294v1.2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005060645"},{"key":"2026040108501076000_2026.03.26.714294v1.3","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M405079200"},{"key":"2026040108501076000_2026.03.26.714294v1.4","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00243.2011"},{"key":"2026040108501076000_2026.03.26.714294v1.5","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2020101512"},{"key":"2026040108501076000_2026.03.26.714294v1.6","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.117.10156"},{"key":"2026040108501076000_2026.03.26.714294v1.7","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.114.05099"},{"key":"2026040108501076000_2026.03.26.714294v1.8","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00686.2009"},{"key":"2026040108501076000_2026.03.26.714294v1.9","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000091235.94914.75"},{"key":"2026040108501076000_2026.03.26.714294v1.10","doi-asserted-by":"publisher","DOI":"10.1124\/pr.119.017533"},{"key":"2026040108501076000_2026.03.26.714294v1.11","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2015.00115"},{"key":"2026040108501076000_2026.03.26.714294v1.12","doi-asserted-by":"publisher","DOI":"10.1210\/en.2014-1257"},{"key":"2026040108501076000_2026.03.26.714294v1.13","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2017.00120"},{"key":"2026040108501076000_2026.03.26.714294v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20560-y"},{"key":"2026040108501076000_2026.03.26.714294v1.15","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000033522.37861.69"},{"key":"2026040108501076000_2026.03.26.714294v1.16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02591.x"},{"key":"2026040108501076000_2026.03.26.714294v1.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2015.02.013"},{"key":"2026040108501076000_2026.03.26.714294v1.18","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016111210"},{"key":"2026040108501076000_2026.03.26.714294v1.19","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-021-03028-1"},{"key":"2026040108501076000_2026.03.26.714294v1.20","doi-asserted-by":"publisher","DOI":"10.1172\/JCI69608"},{"key":"2026040108501076000_2026.03.26.714294v1.21","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.132898"},{"key":"2026040108501076000_2026.03.26.714294v1.22","doi-asserted-by":"publisher","DOI":"10.1007\/s10557-022-07328-w"},{"key":"2026040108501076000_2026.03.26.714294v1.23","doi-asserted-by":"publisher","DOI":"10.1007\/s40268-022-00386-3"},{"key":"2026040108501076000_2026.03.26.714294v1.24","doi-asserted-by":"publisher","DOI":"10.1007\/s40268-021-00380-1"},{"key":"2026040108501076000_2026.03.26.714294v1.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2013.08.007"},{"key":"2026040108501076000_2026.03.26.714294v1.26","doi-asserted-by":"publisher","DOI":"10.1111\/1744-9987.12412"},{"key":"2026040108501076000_2026.03.26.714294v1.27","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22136885"},{"key":"2026040108501076000_2026.03.26.714294v1.28","doi-asserted-by":"publisher","DOI":"10.1172\/JCI64313"},{"key":"2026040108501076000_2026.03.26.714294v1.29","doi-asserted-by":"publisher","DOI":"10.1038\/71724"},{"key":"2026040108501076000_2026.03.26.714294v1.30","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202002490R"},{"key":"2026040108501076000_2026.03.26.714294v1.31","doi-asserted-by":"publisher","DOI":"10.1038\/nm935"},{"key":"2026040108501076000_2026.03.26.714294v1.32","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00350.2024"},{"key":"2026040108501076000_2026.03.26.714294v1.33","doi-asserted-by":"publisher","DOI":"10.1172\/jci127750"},{"key":"2026040108501076000_2026.03.26.714294v1.34","doi-asserted-by":"publisher","DOI":"10.1016\/bs.mcb.2019.05.008"},{"key":"2026040108501076000_2026.03.26.714294v1.35","doi-asserted-by":"publisher","DOI":"10.1007\/s00264-010-1100-y"},{"key":"2026040108501076000_2026.03.26.714294v1.36","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15446"},{"key":"2026040108501076000_2026.03.26.714294v1.37","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp165"},{"key":"2026040108501076000_2026.03.26.714294v1.38","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2015010047"},{"key":"2026040108501076000_2026.03.26.714294v1.39","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvx061"},{"key":"2026040108501076000_2026.03.26.714294v1.40","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34255-z"},{"key":"2026040108501076000_2026.03.26.714294v1.41","doi-asserted-by":"publisher","DOI":"10.1172\/JCI42004"},{"key":"2026040108501076000_2026.03.26.714294v1.42","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2410830121"},{"key":"2026040108501076000_2026.03.26.714294v1.43","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2023.1058825"},{"key":"2026040108501076000_2026.03.26.714294v1.44","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2022.971219"},{"key":"2026040108501076000_2026.03.26.714294v1.45","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.14123"},{"key":"2026040108501076000_2026.03.26.714294v1.46","doi-asserted-by":"publisher","DOI":"10.1210\/en.2010-0576"},{"key":"2026040108501076000_2026.03.26.714294v1.47","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403518101"},{"key":"2026040108501076000_2026.03.26.714294v1.48","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00320.x"},{"key":"2026040108501076000_2026.03.26.714294v1.49","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1819730116"},{"key":"2026040108501076000_2026.03.26.714294v1.50","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.002"},{"key":"2026040108501076000_2026.03.26.714294v1.51","doi-asserted-by":"publisher","DOI":"10.1038\/nature11263"},{"key":"2026040108501076000_2026.03.26.714294v1.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2019.115237"},{"key":"2026040108501076000_2026.03.26.714294v1.53","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-023-09875-8"},{"key":"2026040108501076000_2026.03.26.714294v1.54","unstructured":"BioAge. (https:\/\/ir.bioagelabs.com\/news-releases\/news-release-details\/bioage-labs-announces-discontinuation-strides-phase-2-clinical, BioAge Labs, 2024)."},{"key":"2026040108501076000_2026.03.26.714294v1.55","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2018.01.013"},{"key":"2026040108501076000_2026.03.26.714294v1.56","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52447-7"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.03.26.714294","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T15:50:24Z","timestamp":1775058624000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.03.26.714294"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,30]]},"references-count":56,"URL":"https:\/\/doi.org\/10.64898\/2026.03.26.714294","relation":{},"subject":[],"published":{"date-parts":[[2026,3,30]]},"subtype":"preprint"}}