Biodegradable Stent with mTOR Inhibitor-Eluting Reduces Progression of Ureteral Stricture
In this study, we investigated the effect of mTOR inhibitor (mTORi) drug-eluting biodegradable stent (DE stent), a putative restenosis-inhibiting device for coronary artery, on thermal-injury-related ureteral stricture in rabbits. In vitro evaluation confirmed the dose-dependent effect of mTORi, i.e...
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doaj-7dd65ae98e12484b80d2dce267d9d5ad2021-06-01T01:13:03ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-01225664566410.3390/ijms22115664Biodegradable Stent with mTOR Inhibitor-Eluting Reduces Progression of Ureteral StrictureDong-Ru Ho0Shih-Horng Su1Pey-Jium Chang2Wei-Yu Lin3Yun-Ching Huang4Jian-Hui Lin5Kuo-Tsai Huang6Wai-Nga Chan7Chih-Shou Chen8Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chiayi 613016, TaiwanDuNing Incorperated, Tustin, CA 92780, USADepartment of Medicine, College of Medicine, Chang Gung University, Taoyuan 333323, TaiwanDivision of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chiayi 613016, TaiwanDivision of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chiayi 613016, TaiwanDivision of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chiayi 613016, TaiwanDivision of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chiayi 613016, TaiwanDivision of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chiayi 613016, TaiwanDivision of Urology, Department of Surgery, Chang Gung Memorial Hospital, Chiayi 613016, TaiwanIn this study, we investigated the effect of mTOR inhibitor (mTORi) drug-eluting biodegradable stent (DE stent), a putative restenosis-inhibiting device for coronary artery, on thermal-injury-related ureteral stricture in rabbits. 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–mesenchymal transition markers, including Smad, α-SMA, and SNAI 1. Ureteral thermal injury resulted in severe ipsilateral hydronephrosis. The levels of type III collagen, Smad, α-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-β 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.https://www.mdpi.com/1422-0067/22/11/5664ureterdrug-eluting stentbiodegradableureteral stricturerapamycinsirolimus |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dong-Ru Ho Shih-Horng Su Pey-Jium Chang Wei-Yu Lin Yun-Ching Huang Jian-Hui Lin Kuo-Tsai Huang Wai-Nga Chan Chih-Shou Chen |
spellingShingle |
Dong-Ru Ho Shih-Horng Su Pey-Jium Chang Wei-Yu Lin Yun-Ching Huang Jian-Hui Lin Kuo-Tsai Huang Wai-Nga Chan Chih-Shou Chen Biodegradable Stent with mTOR Inhibitor-Eluting Reduces Progression of Ureteral Stricture International Journal of Molecular Sciences ureter drug-eluting stent biodegradable ureteral stricture rapamycin sirolimus |
author_facet |
Dong-Ru Ho Shih-Horng Su Pey-Jium Chang Wei-Yu Lin Yun-Ching Huang Jian-Hui Lin Kuo-Tsai Huang Wai-Nga Chan Chih-Shou Chen |
author_sort |
Dong-Ru Ho |
title |
Biodegradable Stent with mTOR Inhibitor-Eluting Reduces Progression of Ureteral Stricture |
title_short |
Biodegradable Stent with mTOR Inhibitor-Eluting Reduces Progression of Ureteral Stricture |
title_full |
Biodegradable Stent with mTOR Inhibitor-Eluting Reduces Progression of Ureteral Stricture |
title_fullStr |
Biodegradable Stent with mTOR Inhibitor-Eluting Reduces Progression of Ureteral Stricture |
title_full_unstemmed |
Biodegradable Stent with mTOR Inhibitor-Eluting Reduces Progression of Ureteral Stricture |
title_sort |
biodegradable stent with mtor inhibitor-eluting reduces progression of ureteral stricture |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-05-01 |
description |
In this study, we investigated the effect of mTOR inhibitor (mTORi) drug-eluting biodegradable stent (DE stent), a putative restenosis-inhibiting device for coronary artery, on thermal-injury-related ureteral stricture in rabbits. 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–mesenchymal transition markers, including Smad, α-SMA, and SNAI 1. Ureteral thermal injury resulted in severe ipsilateral hydronephrosis. The levels of type III collagen, Smad, α-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-β 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. |
topic |
ureter drug-eluting stent biodegradable ureteral stricture rapamycin sirolimus |
url |
https://www.mdpi.com/1422-0067/22/11/5664 |
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