{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T14:45:44Z","timestamp":1778942744190,"version":"3.51.4"},"reference-count":31,"publisher":"American Physiological Society","issue":"1","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China (NSFC)","doi-asserted-by":"publisher","award":["81170662;81470964;81522010"],"award-info":[{"award-number":["81170662;81470964;81522010"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China (NSFC)","doi-asserted-by":"publisher","award":["31200872;81570671"],"award-info":[{"award-number":["31200872;81570671"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China (NSFC)","doi-asserted-by":"publisher","award":["30900682"],"award-info":[{"award-number":["30900682"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003819","name":"Natural Science Foundation of Hubei Province (Hubei Provincial Natural Science Foundation)","doi-asserted-by":"publisher","award":["2013CFA026"],"award-info":[{"award-number":["2013CFA026"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Wuhan Science and Technology Bureau","award":["2015060101010039"],"award-info":[{"award-number":["2015060101010039"]}]},{"name":"Doctoral Fund from Ministry of Education of China","award":["20130142110064"],"award-info":[{"award-number":["20130142110064"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2016,7,1]]},"abstract":"<jats:p>MAD2B, an anaphase-promoting complex\/cyclosome (APC\/C) inhibitor and a small subunit of DNA polymerase \u03b6, is indispensible for mitotic checkpoint control and DNA repair. Previously, we established that MAD2B is expressed in glomerular and tubulointerstitial compartments and participates in high glucose-induced podocyte injury. However, its role in other renal diseases remains elusive. In the present study, we aim to illustrate the potential role of MAD2B in the pathogenesis of renal fibrosis. By immunofluorescence and Western blotting, we found MAD2B expression is obviously increased in tubulointerstitial fibrosis (TIF) patients and unilateral ureteral obstruction (UUO) mice. It is widely accepted that resident fibroblasts are the major source of collagen-producing myofibroblasts during TIF. Therefore, we evaluated the level of MAD2B in fibroblasts (NRK-49F) exposed to transforming growth factor (TGF)-\u03b21 by immunoblotting and revealed that MAD2B is upregulated in a time-dependent manner. Intriguingly, SnoN, a transcriptional repressor of the TGF-\u03b21\/Smad signaling pathway, is decreased in TGF-\u03b21-treated fibroblasts as well as the kidney cortex from TIF patients and UUO mice. Either in vitro or in vivo, local genetic depletion of MAD2B by lentiviral transfection could preserve SnoN abundance and suppress Smad3 phosphorylation, which finally dampens fibroblast activation, ECM accumulation, and alleviates the severity of TIF. However, the ubiquitin ligase APC\/C is not involved in the MAD2B-mediated SnoN decline, although this process is ubiquitination dependent. In conclusion, our observation proposes that besides cell cycle management, MAD2B has a profibrotic role during fibroblast activation and TIF by suppressing SnoN expression. Targeting the MAD2B-SnoN pathway is a promising intervention for TIF.<\/jats:p>","DOI":"10.1152\/ajprenal.00600.2015","type":"journal-article","created":{"date-parts":[[2016,5,3]],"date-time":"2016-05-03T17:56:41Z","timestamp":1462298201000},"page":"F207-F216","source":"Crossref","is-referenced-by-count":11,"title":["MAD2B-mediated SnoN downregulation is implicated in fibroblast activation and tubulointerstitial fibrosis"],"prefix":"10.1152","volume":"311","author":[{"given":"Hui","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Di","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun-Tao","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua-Jun","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pan","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang-Fang","family":"He","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.898701"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-3602"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.4161\/cc.23214"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2008.324"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3299"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0400035101"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2014.07.001"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-011-1772-6"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00243.2012"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2008.00925.x"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2008.699"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201302060"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2011.149"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000106015.29070.E7"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2014.287"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015128"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.12229"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.6.4391"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/cas.12390"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.22155"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201591697"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3061-07.2008"},{"key":"B23","doi-asserted-by":"crossref","first-page":"2822","DOI":"10.1101\/gad.912901","volume":"15","author":"Stroschein SL","year":"2001","journal-title":"Genes Dev"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5440.771"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00409.2014"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005101055"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00382-3"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/nature14328"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000099373.33259.B2"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2010.3091"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2010.11.009"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00600.2015","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,19]],"date-time":"2022-06-19T18:19:14Z","timestamp":1655662754000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.00600.2015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,7,1]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,7,1]]}},"alternative-id":["10.1152\/ajprenal.00600.2015"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00600.2015","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7,1]]}}}