Claudia Janssen1, Ralph Buttyan2, Chun Y Seow3, Wolfgang Jäger4, Dennis Solomon3, Ladan Fazli2, Ben H Chew5, Dirk Lange6. 1. Department of Urologic Sciences, The Stone Centre at Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada; Department of Urology, Johannes Gutenberg University, Mainz, Germany. 2. Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada. 3. Department of Pathology and Laboratory Medicine, James Hogg Research Centre, St. Paul Hospital/Providence Health Care, University of British Columbia, Vancouver, BC, Canada. 4. Department of Urology, Johannes Gutenberg University, Mainz, Germany; Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada. 5. Department of Urologic Sciences, The Stone Centre at Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada. 6. Department of Urologic Sciences, The Stone Centre at Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada. Electronic address: dlange@mail.ubc.ca.
Abstract
OBJECTIVE: To better understand the effects of double J stenting on ureteral physiology and function. MATERIALS AND METHODS: In total, 24 pigs were stented cystoscopically unilaterally for 48 hours, 1, 2, 4, and 7 weeks. Controls consisted of un-stented animals (n = 4) or the contralateral un-stented ureter in pigs. Ureters were harvested and tested in tissue baths to evaluate their contractility. Ureteral inflammation and expression of Sonic Hedgehog (Shh) and the transcriptional activator Gli1 (the downstream target of active Hedgehog signaling) were assessed histologically and by immunohistochemistry, respectively. RESULTS: Indwelling ureteral stents were found to abolish normal ureteral function in all animals. Specifically, ureteral smooth muscle (SM) activity was significantly diminished within 48 hours after stenting and persisted at the 1-week time point. Furthermore, ureteral SM dysfunction was associated with increasing ureteral dilation due to the indwelling stent. Simultaneously, we observed a loss of Gli1 expression in SM cells, with a concomitant increase in ureteral inflammation. Expression of Shh was restricted to the urothelium and was not different between controls, stented, and contralateral ureters. CONCLUSION: Stent-induced aperistalsis was associated with diminished SM contractility, increased tissue inflammation, and reduced Gli1 expression in ureteral SM cells, independent of Shh expression. The present study is the first to show that indwelling stents negatively affect ureteral SM activity and identify a role for specific molecular mechanisms involved.
OBJECTIVE: To better understand the effects of double J stenting on ureteral physiology and function. MATERIALS AND METHODS: In total, 24 pigs were stented cystoscopically unilaterally for 48 hours, 1, 2, 4, and 7 weeks. Controls consisted of un-stented animals (n = 4) or the contralateral un-stented ureter in pigs. Ureters were harvested and tested in tissue baths to evaluate their contractility. Ureteral inflammation and expression of Sonic Hedgehog (Shh) and the transcriptional activator Gli1 (the downstream target of active Hedgehog signaling) were assessed histologically and by immunohistochemistry, respectively. RESULTS: Indwelling ureteral stents were found to abolish normal ureteral function in all animals. Specifically, ureteral smooth muscle (SM) activity was significantly diminished within 48 hours after stenting and persisted at the 1-week time point. Furthermore, ureteral SM dysfunction was associated with increasing ureteral dilation due to the indwelling stent. Simultaneously, we observed a loss of Gli1 expression in SM cells, with a concomitant increase in ureteral inflammation. Expression of Shh was restricted to the urothelium and was not different between controls, stented, and contralateral ureters. CONCLUSION: Stent-induced aperistalsis was associated with diminished SM contractility, increased tissue inflammation, and reduced Gli1 expression in ureteral SM cells, independent of Shh expression. The present study is the first to show that indwelling stents negatively affect ureteral SM activity and identify a role for specific molecular mechanisms involved.
Authors: Noor Buchholz; Alberto Budia; Julia de la Cruz; Wolfgang Kram; Owen Humphreys; Meital Reches; Raquel Valero Boix; Federico Soria Journal: Polymers (Basel) Date: 2022-04-19 Impact factor: 4.967