{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T17:20:21Z","timestamp":1782753621079,"version":"3.54.5"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,12,21]],"date-time":"2018-12-21T00:00:00Z","timestamp":1545350400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"VA Rehab R&D Award","award":["1I01RX001694-01A2"],"award-info":[{"award-number":["1I01RX001694-01A2"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurourology and Urodynamics"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Prior studies demonstrate increased incidence of urinary incontinence (UI) in the geriatric population which affects their quality of life. Pathophysiology of UI in the geriatric population and the underlying molecular mechanisms are still unclear. To elucidate these mechanisms, we performed a pre\u2010clinical study in a rabbit model and the objectives were to (i) determine the effect of aging as well as multiparity on urethral sphincter muscle thickness and urethral closing pressure (UCP); (ii) examine the role of fibrosis and atrophy; and (iii) elucidate the molecular pathways that mediate fibrosis and atrophy in the urethral tissue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>New Zealand White female rabbits (<jats:italic>n<\/jats:italic>\u2009=\u20096 each; young 6\u201012 months and old over 30 months of age) were anesthetized and urethral muscle thickness and sphincter closure function were measured. Rabbits were then sacrificed and urethral tissues (bladder neck and mid\u2010urethra) were collected to process for immunostaining as well as for molecular studies for markers for fibrosis (\u03b2\u2010catenin which is an important mediator of Wnt signaling, Collagen\u20101, and TGF\u2010\u03b2) and atrophy (MuRF\u20101).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our studies showed a significant decrease in the urethral sphincter muscle thickness and closure function with age. Age\u2010related increase in protein and mRNA expression levels of fibrosis, as well as atrophy markers were observed in the bladder neck and mid\u2010urethral tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Age and multiparity related increase in fibrosis and atrophy of urethral sphincter muscles may contribute to impaired urethral closure function seen in old animals.<\/jats:p><\/jats:sec>","DOI":"10.1002\/nau.23889","type":"journal-article","created":{"date-parts":[[2018,12,21]],"date-time":"2018-12-21T22:38:10Z","timestamp":1545431890000},"page":"607-614","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Age and multiparity related urethral sphincter muscle dysfunction in a rabbit model: Potential roles of TGF\u2010\u03b2 and Wnt\u2010\u03b2 catenin signaling pathways"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4188-1628","authenticated-orcid":false,"given":"Mahadevan R.","family":"Rajasekaran","sequence":"first","affiliation":[{"name":"Department of Urology San Diego VA Health Care System &amp; University of California San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnny","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Urology San Diego VA Health Care System &amp; University of California San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"My\u2010Uyen (Lilly)","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Urology San Diego VA Health Care System &amp; University of California San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaozhi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology San Diego VA Health Care System &amp; University of California San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Albo","sequence":"additional","affiliation":[{"name":"Department of Urology San Diego VA Health Care System &amp; University of California San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valmik","family":"Bhargava","sequence":"additional","affiliation":[{"name":"Division of Cardiology San Diego VA Health Care System &amp; University of California San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,12,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.1990.tb03502.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005392-200102000-00013"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa021788"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.20888"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2003.10.080"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2008.01.098"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2012.06.001"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)02588-X"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.7863\/jum.2004.23.5.631"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00209.2017"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201600502R"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3727\/105221614X13919976902138"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1734"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1515\/hsz-2017-0217"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00192-014-2540-5"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-01131-6"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0945-053X(98)90122-6"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.234369"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M413367200"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)67106-6"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-9384(01)00638-2"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1144090"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2807"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2277"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00204.2014"}],"container-title":["Neurourology and Urodynamics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fnau.23889","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/nau.23889","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/nau.23889","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/nau.23889","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T22:44:19Z","timestamp":1694040259000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/nau.23889"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,21]]},"references-count":25,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,2]]}},"alternative-id":["10.1002\/nau.23889"],"URL":"https:\/\/doi.org\/10.1002\/nau.23889","archive":["Portico"],"relation":{},"ISSN":["0733-2467","1520-6777"],"issn-type":[{"value":"0733-2467","type":"print"},{"value":"1520-6777","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,21]]},"assertion":[{"value":"2018-09-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}