{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T01:08:35Z","timestamp":1788916115084,"version":"build-2803163510"},"reference-count":59,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,9,17]],"date-time":"2019-09-17T00:00:00Z","timestamp":1568678400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004824","name":"Dansk Nefrologisk Selskab","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004824","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009047","name":"Strategic Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009047","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004196","name":"Odense Universitetshospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Activation of sodium reabsorption by urinary proteases has been implicated in sodium retention associated with nephrotic syndrome. The study was designed to test the hypothesis that nephrotic proteinuria in mice after conditional deletion of podocin leads to urokinase\u2010dependent, amiloride\u2010sensitive plasmin\u2010mediated sodium and water retention.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Ten days after podocin knockout, urine and faeces were collected for 10\u00a0days in metabolic cages and analysed for electrolytes, plasminogen, protease activity and ability to activate \u03b3ENaC by patch clamp and western blot. Mice were treated with amiloride (2.5\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup> for 2\u00a0days and 10\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup> for 2\u00a0days) or an anti\u2010urokinase\u2010type plasminogen activator (uPA) targeting antibody (120\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>\/24\u00a0h) and compared to controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twelve days after deletion, podocin\u2010deficient mice developed significant protein and albuminuria associated with increased body wt, ascites, sodium accumulation and suppressed plasma renin. This was associated with increased urinary excretion of plasmin and plasminogen that correlated with albumin excretion, urine protease activity co\u2010migrating with active plasmin, and the ability of urine to induce an amiloride\u2010sensitive inward current in M1 cells in vitro. Amiloride treatment in podocin\u2010deficient mice resulted in weight loss, increased sodium excretion, normalization of sodium balance and prevention of the activation of plasminogen to plasmin in urine in a reversible way. Administration of uPA targeting antibody abolished urine activation of plasminogen, attenuated sodium accumulation and prevented cleavage of \u03b3ENaC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Nephrotic range glomerular proteinuria leads to urokinase\u2010dependent intratubular plasminogen activation and \u03b3ENaC cleavage which contribute to sodium accumulation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.13362","type":"journal-article","created":{"date-parts":[[2019,8,19]],"date-time":"2019-08-19T07:45:03Z","timestamp":1566200703000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Urokinase\u2010type plasminogen activator contributes to amiloride\u2010sensitive sodium retention in nephrotic range glomerular proteinuria in mice"],"prefix":"10.1111","volume":"227","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0526-7874","authenticated-orcid":false,"given":"Gitte R.","family":"Hinrichs","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, Cardiovascular and Renal Research University of Southern Denmark Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Weyer","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Aarhus University Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulla G.","family":"Friis","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Cardiovascular and Renal Research University of Southern Denmark Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6590-7103","authenticated-orcid":false,"given":"Per","family":"Svenningsen","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Cardiovascular and Renal Research University of Southern Denmark Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida K.","family":"Lund","sequence":"additional","affiliation":[{"name":"The Finsen Laboratory Rigshospitalet Copenhagen Denmark"},{"name":"Biotech Research &amp; Innovation Centre (BRIC) University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikke","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Aarhus University Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e9raldine","family":"Mollet","sequence":"additional","affiliation":[{"name":"Laboratory of Hereditary Kidney Diseases Imagine Institute Inserm, U1163 Paris Descartes\u2010Sorbonne Paris Cit\u00e9 University Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Antignac","sequence":"additional","affiliation":[{"name":"Laboratory of Hereditary Kidney Diseases Imagine Institute Inserm, U1163 Paris Descartes\u2010Sorbonne Paris Cit\u00e9 University Paris France"},{"name":"Department of Genetics Necker Hospital Assistance Publique\u2010H\u00f4pitaux de Paris Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus","family":"Bistrup","sequence":"additional","affiliation":[{"name":"Department of Nephrology Odense University Hospital Odense Denmark"},{"name":"Department of Clinical Research University of Southern Denmark Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7607-213X","authenticated-orcid":false,"given":"Boye L.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Cardiovascular and Renal Research University of Southern Denmark Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Birn","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Aarhus University Aarhus Denmark"},{"name":"Department of Renal Medicine Aarhus University Hospital Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,9,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ackd.2014.11.006"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-91-5-688"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfs527"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI110756"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116328"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1042\/cs0800599"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V114604"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008040364"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V123598"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C400080200"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307003200"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M610636200"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-013-2439-2"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.112.198879"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2017.07.023"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013111173"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M805676200"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00138.2015"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-89-21833"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1711690115"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2000.00342.x"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00694922"},{"issue":"3","key":"e_1_2_7_24_1","first-page":"481","article-title":"Focal and segmental glomerulosclerosis following a single intravenous dose of puromycin aminonucleoside","volume":"122","author":"Diamond JR","year":"1986","journal-title":"Am J Pathol"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1988.3"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1004"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI20402"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2009.03477.x"},{"issue":"16","key":"e_1_2_7_29_1","first-page":"4592","article-title":"Doxorubicin treatment in vivo causes cytochrome C release and cardiomyocyte apoptosis, as well as increased mitochondrial efficiency, superoxide dismutase activity, and Bcl\u20102: Bax ratio","volume":"62","author":"Childs AC","year":"2002","journal-title":"Can Res"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.21570"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2009040379"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M801924200"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012746"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.792"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/74166"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13249"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/159779a0"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.3109\/00016348009155439"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfu402"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000000216"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/39329"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00157.2014"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00133.2012"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14387"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00321.2009"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.12261115"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0000000000000479"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(87)80039-X"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jash.2014.09.019"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000000967"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00126.2014"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.623496"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcped.2004.03.029"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2016.08.027"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12882-018-0916-3"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2017.05.008"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13286"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-201X.2005.01428.x"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-39-5-816"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2013.218"}],"container-title":["Acta Physiologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apha.13362","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/apha.13362","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apha.13362","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T03:09:26Z","timestamp":1693364966000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apha.13362"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,17]]},"references-count":59,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["10.1111\/apha.13362"],"URL":"https:\/\/doi.org\/10.1111\/apha.13362","archive":["Portico"],"relation":{},"ISSN":["1748-1708","1748-1716"],"issn-type":[{"value":"1748-1708","type":"print"},{"value":"1748-1716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,17]]},"assertion":[{"value":"2019-02-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-09-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13362"}}