{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:11:08Z","timestamp":1772118668959,"version":"3.50.1"},"reference-count":25,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2017,2,21]],"date-time":"2017-02-21T00:00:00Z","timestamp":1487635200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100011912","name":"Taipei Veterans General Hospital","doi-asserted-by":"crossref","award":["V104C-189"],"award-info":[{"award-number":["V104C-189"]}],"id":[{"id":"10.13039\/501100011912","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurourology and Urodynamics"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:sec>\n                    <jats:title>AIMS<\/jats:title>\n                    <jats:p>To investigate the pathogenic role of activation of the mammalian target of the rapamycin (mTOR) in the ketamine induced microvascular injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Twenty\u2010three patients with ketamine\u2010induced cystitis (KC) and 16 control volunteers were recruited. Bladder tissues were obtained from both groups by cystoscopic biopsies. Phospho\u2010S6 ribosomal protein (p\u2010S6RP), an end product of the mTOR pathway, was stained in the urinary bladder from both groups. Endothelial cells of the urinary bladder (HBdMECs) were examined to investigate the in vitro activation of the mTOR pathway and the co\u2010expression of the endothelial marker (cluster of differentiation 31 [CD31]) and the mesenchymal marker (fibroblast\u2010specific protein 1 [FSP\u20101]).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Expression of p\u2010S6RP increased significantly after ketamine exposure, especially in the vesical microvessels of KC patients. In HBdMECs treated with 100\u2009\u00b5M Ketamine, time\u2010dependent activation of the mTOR pathway occurred, with significantly increased levels of the phosphorylated forms of mTOR at 30\u2009min and of S6RP and p70S6 kinase (p70S6K) at 6\u2009h. The increased level of p\u2010S6RP returned to baseline within 2 days after ketamine exposure. The co\u2010expression of CD31 and FSP\u20101 implied that EndMT was present in HBdMECs at 7 days after ketamine treatment, while TGF\u2010\u03b21 facilitated significant up\u2010regulation of FSP\u20101 at 1 day after treatment. Furthermore, when the mTOR inhibitor rapamycin was administered with ketamine to the HBdMECs, the expression of FSP\u20101 decreased significantly.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>Ketamine induces activation of the mTOR pathway and subsequent mesenchymal phenotypic expression (FSP1) in HBdMECs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/nau.23234","type":"journal-article","created":{"date-parts":[[2017,2,21]],"date-time":"2017-02-21T12:03:54Z","timestamp":1487678634000},"page":"1988-1995","source":"Crossref","is-referenced-by-count":5,"title":["Activation of the mTOR dependent signaling pathway underlies ketamine\u2010induced uropathy"],"prefix":"10.1002","volume":"36","author":[{"given":"Chih\u2010Chieh","family":"Lin","sequence":"first","affiliation":[{"name":"Institute of Clinical Medicine National Yang\u2010Ming University Taipei Taiwan"},{"name":"Department of Urology School of Medicine National Yang\u2010Ming University Taipei Taiwan"},{"name":"Department of Urology Taipei Veterans General Hospital Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"An\u2010Hang","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine National Yang\u2010Ming University Taipei Taiwan"},{"name":"Department of Pathology and Laboratory Medicine Taipei Veterans General Hospital Taipei Taiwan"},{"name":"Department of Pathology School of Medicine National Yang\u2010Ming University Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex Tong\u2010Long","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine National Yang\u2010Ming University Taipei Taiwan"},{"name":"Department of Urology School of Medicine National Yang\u2010Ming University Taipei Taiwan"},{"name":"Department of Urology Taipei Veterans 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