{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T18:24:53Z","timestamp":1778869493700,"version":"3.51.4"},"reference-count":27,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T00:00:00Z","timestamp":1564531200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T00:00:00Z","timestamp":1564531200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["31003A_138517"],"award-info":[{"award-number":["31003A_138517"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The\n                    <jats:italic>NPHS2<\/jats:italic>\n                    gene, encoding the slit diaphragm protein podocin, accounts for genetic and sporadic forms of nephrotic syndrome (NS). Patients with NS often present symptoms of volume retention, such as oedema formation or hypertension. The primary dysregulation in sodium handling involves an inappropriate activation of the epithelial sodium channel, ENaC. Plasma proteases in a proteinuria\u2010dependent fashion have been made responsible; however, referring to the timeline of symptoms occurring and underlying mechanisms, contradictory results have been published. Characterizing the mouse model of podocyte inactivation of\n                    <jats:italic>NPHS2<\/jats:italic>\n                    (Nphs2\n                    <jats:sup>\u2206pod<\/jats:sup>\n                    ) with respect to volume handling and proteinuria revealed that sodium retention, hypertension and gross proteinuria appeared sequentially in a chronological order. Detailed analysis of Nphs2\n                    <jats:sup>\u2206pod<\/jats:sup>\n                    during early sodium retention, revealed increased expression of full\u2010length ENaC subunits and \u03b1ENaC cleavage product with concomitant increase in ENaC activity as tested by amiloride application, and augmented collecting duct Na\n                    <jats:sup>+<\/jats:sup>\n                    \/K\n                    <jats:sup>+<\/jats:sup>\n                    \u2010ATPase expression. Urinary proteolytic activity was increased and several proteases were identified by mass spectrometry including cathepsin B, which was found to process \u03b1ENaC. Renal expression levels of precursor and active cathepsin B were increased and could be localized to glomeruli and intercalated cells. Inhibition of cathepsin B prevented hypertension. With the appearance of gross proteinuria, plasmin occurs in the urine and additional cleavage of \u03b3ENaC is encountered. In conclusion, characterizing the volume handling of Nphs2\n                    <jats:sup>\u2206pod<\/jats:sup>\n                    revealed early sodium retention occurring independent to aberrantly filtered plasma proteases. As an underlying mechanism cathepsin B induced \u03b1ENaC processing leading to augmented channel activity and hypertension was identified.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.14387","type":"journal-article","created":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T01:53:14Z","timestamp":1564624394000},"page":"6543-6553","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Cathepsin B increases ENaC activity leading to hypertension early in nephrotic syndrome"],"prefix":"10.1111","volume":"23","author":[{"given":"Alexey","family":"Larionov","sequence":"first","affiliation":[{"name":"Institute of Anatomy, Department of Medicine University of Fribourg Fribourg Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eileen","family":"Dahlke","sequence":"additional","affiliation":[{"name":"Institute of Anatomy Christian Albrechts\u2010University Kiel Kiel 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