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In vitro evaluation confirmed the dose-dependent effect of mTORi, i.e., rapamycin, on fibrotic markers in ureteral component cell lines. Upper ureteral fibrosis was induced by ureteral thermal injury in open surgery, which was followed by insertion of biodegradable stents, with or without rapamycin drug-eluting. Immunohistochemistry and Western blotting were performed 4 weeks after the operation to determine gross anatomy changes, collagen deposition, expression of epithelial\u2013mesenchymal transition markers, including Smad, \u03b1-SMA, and SNAI 1. Ureteral thermal injury resulted in severe ipsilateral hydronephrosis. The levels of type III collagen, Smad, \u03b1-SMA, and SNAI 1 were increased 28 days after ureteral thermal injury. Treatment with mTORi-eluting biodegradable stents significantly attenuated thermal injury-induced urinary tract obstruction and reduced the level of fibrosis proteins, i.e., type III collagen. TGF-\u03b2 and EMT signaling pathway markers, Smad and SNAI 1, were significantly modified in DE stent-treated thermal-injury-related ureteral stricture rabbits. These results suggested that intra-ureteral administration of rapamycin by DE stent provides modification of fibrosis signaling pathway, and inhibiting mTOR may result in fibrotic process change.<\/jats:p>","DOI":"10.3390\/ijms22115664","type":"journal-article","created":{"date-parts":[[2021,5,26]],"date-time":"2021-05-26T10:30:32Z","timestamp":1622025032000},"page":"5664","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Biodegradable Stent with mTOR Inhibitor-Eluting Reduces Progression of Ureteral Stricture"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1805-0538","authenticated-orcid":false,"given":"Dong-Ru","family":"Ho","sequence":"first","affiliation":[{"name":"Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan"},{"name":"Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan"},{"name":"Department of Nursing, Chang Gung University of Science and Technology, Chiayi 613016, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Horng","family":"Su","sequence":"additional","affiliation":[{"name":"DuNing Incorperated, Tustin, CA 92780, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pey-Jium","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Yu","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Ching","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Hui","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo-Tsai","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai-Nga","family":"Chan","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5785-2373","authenticated-orcid":false,"given":"Chih-Shou","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1089\/089277901317203047","article-title":"Management of malignant extrinsic compression of the ureter by simultaneous placement of two ipsilateral ureteral stents","volume":"15","author":"Rotariu","year":"2001","journal-title":"J. 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