{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T03:45:13Z","timestamp":1773719113740,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,3,22]],"date-time":"2017-03-22T00:00:00Z","timestamp":1490140800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23791763"],"award-info":[{"award-number":["23791763"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["26462446"],"award-info":[{"award-number":["26462446"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int J of Urology"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>To examine the inhibitory effects of tumor necrosis factor\u2010\u03b1 on myogenic differentiation of human urethral rhabdosphincter cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A rhabdosphincter sample was obtained from a patient who underwent total cystectomy. To expand the lifespan of the primary cultured cells, rhabdosphincter myogenic cells were immortalized with mutated cyclin\u2010dependent kinase 4, cyclin D1 and telomerase. The differential potential of the cells was investigated. The transfected human <jats:styled-content style=\"fixed-case\">rhabdosphincter<\/jats:styled-content> cells were induced for myogenic differentiation with recombinant human tumor necrosis factor\u2010\u03b1 and\/or the tumor necrosis factor\u2010\u03b1 antagonist etanercept at different concentrations, and activation of signaling pathways was monitored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Human <jats:styled-content style=\"fixed-case\">rhabdosphincter<\/jats:styled-content> cells were selectively cultured for at least 40 passages. Molecular analysis confirmed the expression of myosin heavy chain, which is a specific marker of differentiated muscle cells, significantly increased after differentiation induction. Although tumor necrosis factor\u2010\u03b1 treatment reduced the <jats:styled-content style=\"fixed-case\">myosin heavy chain<\/jats:styled-content> expression in a concentration\u2010dependent manner, etanercept inhibited this suppression. Tumor necrosis factor\u2010\u03b1 suppressed phosphorylation of protein kinase B and p38, whereas etanercept pretreatment promoted phosphorylation and <jats:styled-content style=\"fixed-case\">myosin heavy chain<\/jats:styled-content> expression in a concentration\u2010dependent manner.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Tumor necrosis factor\u2010\u03b1 inhibits differentiation of urethral rhabdosphincter cells in part through the p38 mitogen\u2010activated protein kinase and phosphoinositide 3\u2010kinase pathways. Inhibition of tumor necrosis factor\u2010\u03b1 might be a useful strategy to treat stress urinary incontinence.<\/jats:p><\/jats:sec>","DOI":"10.1111\/iju.13330","type":"journal-article","created":{"date-parts":[[2017,3,23]],"date-time":"2017-03-23T21:58:31Z","timestamp":1490306311000},"page":"461-467","source":"Crossref","is-referenced-by-count":13,"title":["Tumor necrosis factor\u2010alpha inhibits differentiation of myogenic cells in human urethral rhabdosphincter"],"prefix":"10.1111","volume":"24","author":[{"given":"Mayuka","family":"Shinohara","sequence":"first","affiliation":[{"name":"Department of Oncological Science (Urology) Oita University Faculty of Medicine Yufu Oita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiro","family":"Sumino","sequence":"additional","affiliation":[{"name":"Department of Oncological Science (Urology) Oita University Faculty of Medicine Yufu Oita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuminori","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Oncological Science (Urology) Oita University Faculty of Medicine Yufu Oita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tohru","family":"Kiyono","sequence":"additional","affiliation":[{"name":"Division of Carcinogenesis and Cancer Prevention National Cancer Center Research Institute Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naohiro","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine Institute National Center for Geriatrics and Gerontology Obu Aichi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiromitsu","family":"Mimata","sequence":"additional","affiliation":[{"name":"Department of Oncological Science (Urology) Oita University Faculty of Medicine Yufu Oita Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,3,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2008.01.098"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.20888"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1442-2042.2012.02976.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)67106-6"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.10387"},{"key":"e_1_2_8_7_1","first-page":"E294","article-title":"Advancing age and insulin resistance: role of plasma tumor necrosis factor\u2010alpha","volume":"275","author":"Paolisso G","year":"1998","journal-title":"Am. 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