{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T22:08:19Z","timestamp":1789596499758,"version":"build-2803163510"},"reference-count":31,"publisher":"American Diabetes Association","issue":"12","license":[{"start":{"date-parts":[[2016,11,22]],"date-time":"2016-11-22T00:00:00Z","timestamp":1479772800000},"content-version":"vor","delay-in-days":98,"URL":"http:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SCHI587\/3,4,6"],"award-info":[{"award-number":["SCHI587\/3,4,6"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,12,1]]},"abstract":"<jats:p>Diabetic nephropathy (DN) is the major cause of end-stage renal disease worldwide. Podocytes are important for glomerular filtration barrier function and maintenance of size selectivity in protein filtration in the kidney. Podocyte damage is the basis of many glomerular diseases characterized by loss of interdigitating foot processes and decreased expression of components of the slit diaphragm. Nephrin, a podocyte-specific protein, is the main component of the slit diaphragm. Loss of nephrin is observed in human and rodent models of diabetic kidney disease. The long isoform of CIN85 (RukL) is a binding partner of nephrin that mediates nephrin endocytosis via ubiquitination in podocytes. Here we demonstrate that the loss of nephrin expression and the onset of proteinuria in diabetic mice correlate with an increased accumulation of ubiquitinated proteins and expression of CIN85\/RukL in podocytes. CIN85\/RukL deficiency preserved nephrin surface expression on the slit diaphragm and reduced proteinuria in diabetic mice, whereas overexpression of CIN85 in zebrafish induced severe edema and disruption of the filtration barrier. Thus, CIN85\/RukL is involved in endocytosis of nephrin in podocytes under diabetic conditions, causing podocyte depletion and promoting proteinuria. CIN85\/RukL expression therefore shows potential to be a novel target for antiproteinuric therapy in diabetes.<\/jats:p>","DOI":"10.2337\/db16-0081","type":"journal-article","created":{"date-parts":[[2016,8,17]],"date-time":"2016-08-17T01:59:34Z","timestamp":1471399174000},"page":"3667-3679","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":45,"title":["CIN85 Deficiency Prevents Nephrin Endocytosis and Proteinuria in Diabetes"],"prefix":"10.2337","volume":"65","author":[{"given":"Beina","family":"Teng","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Schroder","sequence":"additional","affiliation":[{"name":"Mount Desert Island Biological Laboratory, Salisbury Cove, ME"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janina","family":"M\u00fcller-Deile","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiko","family":"Schenk","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynne","family":"Staggs","sequence":"additional","affiliation":[{"name":"Mount Desert Island Biological Laboratory, Salisbury Cove, ME"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irini","family":"Tossidou","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Hannover Medical School, Hannover, 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