{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T23:01:14Z","timestamp":1789599674970,"version":"build-2803163510"},"reference-count":24,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2011,6,28]],"date-time":"2011-06-28T00:00:00Z","timestamp":1309219200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Nephrology"],"published-print":{"date-parts":[[2011,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:bold>Aim:\u2003<\/jats:bold> The relationship between abnormalities of tubular architecture and tubulointerstitial nephritis antigen (TIN\u2010ag) in juvenile nephronophthisis (J\u2010NPH) was evaluated.<\/jats:p><jats:p><jats:bold>Methods:\u2003<\/jats:bold> Sixteen J\u2010NPH patients were examined. Nephrocystin\u20101, TIN\u2010ag, type IV collagen, Fas antigen and the C5b\u20109 complement complex were stained by immunohistochemical methods.<\/jats:p><jats:p><jats:bold>Results:\u2003<\/jats:bold> Renal tubules of patients with J\u2010NPH showed morphological abnormalities of tubular basement membranes (TBM) and frequent apoptosis of tubular epithelial cells. Additionally, the C5b\u20109 complement complex was deposited within the TBM in the absence of immunoglobulin deposition, suggesting complement\u2010dependent TBM injury. Localization of TIN\u2010ag in the TBM of J\u2010NPH patients disclosed a partial defect or discontinuity in 14 of the 16 patients, while type IV collagen immunoreactivity was relatively preserved. These findings suggest that tubulogenesis is disturbed during nephronogenesis in J\u2010NPH patients because of a defect in nephrocystin, an <jats:italic>NPHP<\/jats:italic> gene product. TBM defects induce further morphological abnormalities such as cystic dilation of tubules; as tubular function impairment advances, the incomplete tubules may be injured by C5b\u20109 complement complexes, followed by apoptotic cell death.<\/jats:p><jats:p><jats:bold>Conclusion:\u2003<\/jats:bold> TIN\u2010ag, which is important in early nephrogenesis, lacks normal activity, and vulnerable and incomplete tubules with deficient TIN\u2010ag expression are formed. Removal of these defective tubules by apoptosis combined with the C5b\u20109 complement complex could be the primary reason for progression to end\u2010stage renal disease in J\u2010NPH patients.<\/jats:p>","DOI":"10.1111\/j.1440-1797.2011.01442.x","type":"journal-article","created":{"date-parts":[[2011,1,26]],"date-time":"2011-01-26T09:51:21Z","timestamp":1296035481000},"page":"495-501","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Renal tubular dysgenesis and tubulointerstitial nephritis antigen in juvenile nephronophthisis"],"prefix":"10.1111","volume":"16","author":[{"given":"KEISUKE","family":"SUGIMOTO","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YUTAKA","family":"TAKEMURA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HIDEHIKO","family":"YANAGIDA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SHINSUKE","family":"FUJITA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"TOMOKI","family":"MIYAZAWA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"NAOKI","family":"SAKATA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MITSURU","family":"OKADA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"TSUKASA","family":"TAKEMURA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,6,28]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"499","volume-title":"Diseases of the Kidney","author":"Hildebrandt F","year":"1997"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008050456"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-008-0840-z"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V112270"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng996"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0493-342"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/13.6.1334"},{"key":"e_1_2_6_9_2","first-page":"564","article-title":"Nephronophthisis. 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