{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T19:12:35Z","timestamp":1793473955927,"version":"4.5.0"},"reference-count":42,"publisher":"American Physiological Society","issue":"3","funder":[{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)","doi-asserted-by":"publisher","award":["R01DK103534"],"award-info":[{"award-number":["R01DK103534"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2017,9,1]]},"abstract":"<jats:p>Bladder outlet obstruction (BOO) triggers inflammation in the bladder through the NLRP3 inflammasome. BOO also activates fibrosis, which is largely responsible for the decompensation of the bladder in the chronic state. Because fibrosis can be driven by inflammation, we have explored a role for NLRP3 (and IL-1\u03b2 produced by NLRP3) in the activation and progression of BOO-induced fibrosis. Female rats were divided into five groups: 1) control, 2) sham, 3) BOO + vehicle, 4) BOO + the NLRP3 inhibitor glyburide, or 5) BOO + the IL-1\u03b2 receptor antagonist anakinra. Fibrosis was assessed by Masson\u2019s trichrome stain, collagen secretion via Sirius Red, and protein localization by immunofluorescence. BOO increased collagen production in the bladder, which was blocked by glyburide and anakinra, clearly implicating the NLRP3\/IL-1\u03b2 pathway in fibrosis. The collagen was primarily found in the lamina propria and the smooth muscle, while IL-1 receptor 1 and prolyl 4-hydroylase (an enzyme involved in the intracellular modification of collagen) both localized to the urothelium and the smooth muscle. Lysyl oxidase, the enzyme involved in the final extracellular assembly of mature collagen fibrils, was found to some extent in the lamina propria where its expression was greatly enhanced during BOO. In vitro studies demonstrated isolated urothelial cells from BOO rats secreted substantially more collagen than controls, and collagen expression in control cultures could be directly stimulated by IL-1\u03b2. In summary, NLRP3-derived-IL-1\u03b2 triggers fibrosis during BOO, most likely through an autocrine loop in which IL-1\u03b2 acts on urothelia to drive collagen production.<\/jats:p>","DOI":"10.1152\/ajprenal.00128.2017","type":"journal-article","created":{"date-parts":[[2017,6,7]],"date-time":"2017-06-07T20:10:52Z","timestamp":1496866252000},"page":"F603-F610","source":"Crossref","is-referenced-by-count":47,"title":["Bladder fibrosis during outlet obstruction is triggered through the NLRP3 inflammasome and the production of IL-1\u03b2"],"prefix":"10.1152","volume":"313","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3776-3653","authenticated-orcid":false,"suffix":"Jr.","given":"Francis M.","family":"Hughes","sequence":"first","affiliation":[{"name":"Division of Urology, Department of Surgery, Duke University Medical Center, Durham, North Carolina;"},{"name":"Department of Bioengineering, Clemson University, Clemson, South Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie J.","family":"Sexton","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery, Duke University Medical Center, Durham, North Carolina;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huixia","family":"Jin","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery, Duke University Medical Center, Durham, North Carolina;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vihasa","family":"Govada","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery, Duke University Medical Center, Durham, North Carolina;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Todd","family":"Purves","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery, Duke University Medical Center, Durham, North Carolina;"},{"name":"Department of Pediatrics, Duke University Medical Center, Durham, North Carolina; and"},{"name":"Department of Bioengineering, Clemson University, Clemson, South Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12265471"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1442-2042.1996.tb00573.x"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00273.2012"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)35560-X"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/nau.21078"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2012.09.014"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s00005-009-0024-y"},{"key":"B8","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1002\/9780470122860.ch6","volume":"41","author":"Cardinale GJ","year":"1974","journal-title":"Adv Enzymol Relat Areas Mol Biol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2012.07.019"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(01)80132-3"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.90564.2008"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(01)65553-8"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3893"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2015.12.068"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00297.2013"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10791"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2006.09.019"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2009.02.026"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1007\/s12079-013-0216-4"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0129655"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfp214"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2011.01.048"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/nau.22721"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1007\/s13577-013-0070-y"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.04.007"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200903124"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00564-2015"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpurol.2006.03.011"},{"key":"B29","first-page":"43","volume":"184","author":"Levin RM","year":"1997","journal-title":"Scand J Urol Nephrol Suppl"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1159\/000438843"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2010.09445.x"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/PL00007467"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2009.02.104"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/0168-8278(91)90002-S"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-4295(01)01673-9"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12458"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.19.14139"},{"key":"B38","first-page":"307","volume":"23","author":"Tiggelman AM","year":"1995","journal-title":"J Hepatol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1067\/mlc.2002.128468"},{"key":"B40","first-page":"126","volume":"16","author":"Wang H","year":"2016","journal-title":"Bosn J Basic Med Sci"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.08.037"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/nri1412"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00128.2017","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T12:49:18Z","timestamp":1719233358000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.00128.2017"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,1]]},"references-count":42,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2017,9,1]]}},"alternative-id":["10.1152\/ajprenal.00128.2017"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00128.2017","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,1]]}}}