Biodegradable stent with mtor inhibitor-eluting reduces progression of ureteral stricture

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*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

15 Scopus citations

Abstract

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 fibro-sis 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.

Original languageEnglish
Article number5664
JournalInternational Journal of Molecular Sciences
Volume22
Issue number11
DOIs
StatePublished - 01 06 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Biodegradable
  • Drug-eluting stent
  • Epithelial–mesenchymal transition
  • Fibrosis
  • Mammalian target of rapamycin
  • Rapamycin
  • Sirolimus
  • Ureter
  • Ureteral stricture

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