{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T10:00:05Z","timestamp":1791108005735,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2011,2,3]],"date-time":"2011-02-03T00:00:00Z","timestamp":1296691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2011,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Although protein recapture and catabolismi is known as a key function of kidney proximal tubular cells (PTCs), to date, no single protease has been shown to be required. Asparagine endopeptidase (AEP) is an unusually specific endosomal and lysosomal cysteine protease, expressed at high levels in the PTCs of the mammalian kidney. We report that mice lacking AEP accumulate a discrete set of proteins in their PTC endosomes and lysosomes, which indicates a defect in the normal catabolism of proteins captured from the filtrate. Moreover, the mice develop progressive kidney pathology, including hyperplasia of PTCs, interstitial fibrosis, development of glomerular cysts, and renal pelvis dilation. By 6 mo of age, the glomerular filtration rate in AEP\u2010null mice dropped by almost a factor of 2, and the mice developed proteinuria. We also show that EGF receptor levels are significantly higher in AEP\u2010null PTCs, which likely explains the hyperplasia, and we show that chemical inhibition of AEP activity suppresses down\u2010regulation of the EGF receptor\n                    <jats:italic>in vitro.<\/jats:italic>\n                    Thus, AEP is required for normal protein catabolism by PTCs, and its loss induces proliferative and other abnormalities in the murine kidney, at least in part through defective regulation of the EGF receptor.\u2014Miller, G., Matthews, S. P., Reinheckel, R., Fleming, S., Watts, C. Asparagine endopeptidase is required for normal kidney physiology and homeostasis.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    25, 1606\u20131617 (2011).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.10-172312","type":"journal-article","created":{"date-parts":[[2011,2,3]],"date-time":"2011-02-03T22:56:19Z","timestamp":1296773779000},"page":"1606-1617","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["Asparagine endopeptidase is required for normal kidney physiology and homeostasis"],"prefix":"10.1096","volume":"25","author":[{"given":"Gail","family":"Miller","sequence":"first","affiliation":[{"name":"Division of Cell Biology and Immunology College of Life Sciences University of Dundee Dundee UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen P.","family":"Matthews","sequence":"additional","affiliation":[{"name":"Division of Cell Biology and Immunology College of Life Sciences University of Dundee Dundee UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Reinheckel","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Molekulare Medizin und Zellforschung Albert-Ludwigs-Universit\u00e4t Freiburg Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stewart","family":"Fleming","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology Ninewells Hospital University of Dundee Dundee UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Watts","sequence":"additional","affiliation":[{"name":"Division of Cell Biology and Immunology College of Life Sciences University of Dundee Dundee UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,2,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm778"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.12.8090"},{"key":"e_1_2_6_4_1","first-page":"31","article-title":"Roles for asparagine endopeptidase in class II MHC\u2010restricted antigen processing","author":"Watts C.","year":"2003","journal-title":"Biochem. 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