{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T02:47:00Z","timestamp":1773456420225,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,2,8]],"date-time":"2013-02-08T00:00:00Z","timestamp":1360281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK083299"],"award-info":[{"award-number":["DK083299"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:p>\n                    Bladder urothelium senses and communicates information about bladder fullness. However, the mechanoreceptors that respond to tissue stretch are poorly defined. Integrins are mechanotransducers in other tissues. Therefore, we eliminated \u03b21\u2010integrin selectively in urothelium of mice using Cre\u2010LoxP targeted gene deletion. \u03b21\u2010Integrin localized to basal\/ intermediate urothelial cells by confocal microscopy. \u03b21\u2010Integrin conditional\u2010knockout (\u03b21\u2010cKO) mice lacking urothelial \u03b21\u2010integrin exhibited down\u2010regulation and mislocalization of \u03b13\u2010 and \u03b15\u2010integrins by immunohistochemistry but, surprisingly, had normal morphology, permeability, and transepithelial resistance when compared with Cre\u2010negative littermate controls. \u03b21\u2010cKO mice were incontinent, as judged by random urine leakage on filter paper (4\u2010fold higher spotting,\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.01; 2.5\u2010fold higher urine area percentage,\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05). Urodynamic function assessed by cystometry revealed bladder overfilling with 80% longer intercontractile intervals (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05) and detrusor hyperactivity (3\u2010fold more prevoid contractions,\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05), but smooth muscle contractility remained intact. ATP secretion into the lumen was elevated (49\n                    <jats:italic>vs.<\/jats:italic>\n                    22 nM,\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05), indicating abnormal filling\u2010induced purinergic signaling, and short\u2010circuit currents (measured in Ussing chambers) revealed 2\u2010fold higher stretch\u2010activated ion channel conductances in response to hydrostatic pressure of 1 cmH\n                    <jats:sub>2<\/jats:sub>\n                    O (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05). We conclude that loss of integrin signaling from urothelium results in incontinence and overactive bladder due to abnormal mechanotransduction; more broadly, our findings indicate that urothelium itself directly modulates voiding.\u2014Kanasaki, K., Yu, W., von Bodungen, M., Larigakis, J. D., Kanasaki, M., Ayala de la Pena, F., Kalluri, R., Hill, W.G. Loss of \u03b21\u2010integrin from urothelium results in overactive bladder and incontinence in mice: a mechanosensory rather than structural phenotype.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    27, 1950\u20131961 (2013).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.12-223404","type":"journal-article","created":{"date-parts":[[2013,2,8]],"date-time":"2013-02-08T23:08:44Z","timestamp":1360364924000},"page":"1950-1961","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Loss of \u03b21\u2010integrin from urothelium results in overactive bladder and incontinence in mice: a mechanosensory rather than structural phenotype"],"prefix":"10.1096","volume":"27","author":[{"given":"Keizo","family":"Kanasaki","sequence":"first","affiliation":[{"name":"Division of Matrix Biology Beth Israel Deaconess Medical Center and Harvard Medical School Boston Massachusetts USA"}]},{"given":"Weiqun","family":"Yu","sequence":"additional","affiliation":[{"name":"Division of Nephrology Beth Israel Deaconess Medical Center and Harvard Medical School Boston Massachusetts USA"},{"name":"Laboratory of Voiding Dysfunction, Department of Medicine Beth Israel Deaconess Medical Center and Harvard Medical School Boston Massachusetts USA"}]},{"given":"Maximilian","family":"von Bodungen","sequence":"additional","affiliation":[{"name":"Division of Nephrology Beth Israel Deaconess Medical Center and Harvard Medical School Boston Massachusetts USA"},{"name":"Laboratory of Voiding Dysfunction, Department of Medicine Beth Israel Deaconess Medical Center and Harvard Medical School Boston Massachusetts USA"}]},{"given":"John D.","family":"Larigakis","sequence":"additional","affiliation":[{"name":"Division of Nephrology Beth Israel Deaconess Medical Center and Harvard Medical School Boston Massachusetts USA"},{"name":"Laboratory of Voiding Dysfunction, Department of Medicine Beth Israel Deaconess Medical Center and Harvard Medical School Boston Massachusetts USA"}]},{"given":"Megumi","family":"Kanasaki","sequence":"additional","affiliation":[{"name":"Division of Matrix Biology Beth Israel Deaconess Medical Center and Harvard Medical School Boston Massachusetts USA"}]},{"given":"Francisco Ayala","family":"de la Pena","sequence":"additional","affiliation":[{"name":"Division of Matrix Biology Beth Israel Deaconess Medical Center and Harvard Medical School Boston Massachusetts USA"}]},{"given":"Raghu","family":"Kalluri","sequence":"additional","affiliation":[{"name":"Division of Matrix Biology Beth Israel Deaconess Medical Center and Harvard Medical School Boston Massachusetts USA"}]},{"given":"Warren G.","family":"Hill","sequence":"additional","affiliation":[{"name":"Division of Matrix Biology Beth Israel Deaconess Medical Center and Harvard Medical School Boston Massachusetts USA"},{"name":"Laboratory of Voiding Dysfunction, Department of Medicine Beth Israel Deaconess Medical Center and Harvard Medical School Boston Massachusetts USA"}]}],"member":"311","published-online":{"date-parts":[[2013,2,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2004.08.063"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-540-79090-7_4"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5002439"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00403.2002"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00349.2010"},{"key":"e_1_2_7_7_1","first-page":"1199","article-title":"Expression of growth factors and receptors during specific phases in regenerating urothelium after acute injury in vivo","volume":"145","author":"De Boer W. 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