Yasuhiro Sumino1, Satoru Yoshikawa2, Ken-Ichi Mori1, Hiromitsu Mimata3, Naoki Yoshimura4. 1. Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Department of Urology, Oita University Faculty of Medicine, Oita, Japan. 2. Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. 3. Department of Urology, Oita University Faculty of Medicine, Oita, Japan. 4. Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Electronic address: nyos@pitt.edu.
Abstract
PURPOSE: We examined the functional role of endogenous IGF-1 (insulin-like growth factor-1) in the recovery phase of stress urinary incontinence induced by simulated childbirth trauma using an IGF-1 receptor inhibitor. MATERIALS AND METHODS: Simulated birth trauma was induced by vaginal distension in female Sprague Dawley® rats. The IGF-1 receptor antagonist JB-1 (10 and 100 μg/kg per day) or vehicle was continuously delivered from 1 day before vaginal distension for 7 days using subcutaneous osmotic pumps. Seven, 14 and 21 days after vaginal distension the effect of JB-1 treatment was examined by functional analyses, including leak point and urethral baseline pressure, and urethral responses during passive increments in intravesical pressure, as well as molecular analyses in urethral tissues, including phosphorylation of Akt, apoptotic changes and peripheral nerve density using Western blot and immunohistochemistry. RESULTS: On functional analyses vehicle treated rats with vaginal distension had significantly decreased leak point and urethral baseline pressure, and urethral responses at 7 days, which recovered to the normal level 14 and 21 days after vaginal distension. In the JB-1 treated vaginal distension group leak point and urethral baseline pressure, and urethral responses were still significantly reduced 21 days after vaginal distension. On molecular analyses JB-1 treatment increased apoptotic cells, induced a significant decrease in phosphorylated Akt and prolonged the decrease of peripheral nerve density in urethral tissues. CONCLUSIONS: Suppression of endogenous IGF-1 activity delayed recovery from stress urinary incontinence induced by simulated childbirth trauma in rats. Thus, IGF-1 is likely to be an important endogenous mediator for functional recovery from childbirth related stress urinary incontinence. This suggests that IGF-1 could be an effective target for treating stress urinary incontinence in women.
PURPOSE: We examined the functional role of endogenous IGF-1 (insulin-like growth factor-1) in the recovery phase of stress urinary incontinence induced by simulated childbirth trauma using an IGF-1 receptor inhibitor. MATERIALS AND METHODS: Simulated birth trauma was induced by vaginal distension in female Sprague Dawley® rats. The IGF-1 receptor antagonist JB-1 (10 and 100 μg/kg per day) or vehicle was continuously delivered from 1 day before vaginal distension for 7 days using subcutaneous osmotic pumps. Seven, 14 and 21 days after vaginal distension the effect of JB-1 treatment was examined by functional analyses, including leak point and urethral baseline pressure, and urethral responses during passive increments in intravesical pressure, as well as molecular analyses in urethral tissues, including phosphorylation of Akt, apoptotic changes and peripheral nerve density using Western blot and immunohistochemistry. RESULTS: On functional analyses vehicle treated rats with vaginal distension had significantly decreased leak point and urethral baseline pressure, and urethral responses at 7 days, which recovered to the normal level 14 and 21 days after vaginal distension. In the JB-1 treated vaginal distension group leak point and urethral baseline pressure, and urethral responses were still significantly reduced 21 days after vaginal distension. On molecular analyses JB-1 treatment increased apoptotic cells, induced a significant decrease in phosphorylated Akt and prolonged the decrease of peripheral nerve density in urethral tissues. CONCLUSIONS: Suppression of endogenous IGF-1 activity delayed recovery from stress urinary incontinence induced by simulated childbirth trauma in rats. Thus, IGF-1 is likely to be an important endogenous mediator for functional recovery from childbirth related stress urinary incontinence. This suggests that IGF-1 could be an effective target for treating stress urinary incontinence in women.
Authors: Bradley C Gill; Dan Li Lin; Brian M Balog; Charuspong Dissaranan; Hai-Hong Jiang; Margot S Damaser Journal: SDRP J Biomed Eng Date: 2016-02-05
Authors: Wilke M Post; Joanna Widomska; Hilde Grens; Marieke J H Coenen; Frank M J Martens; Dick A W Janssen; Joanna IntHout; Geert Poelmans; Egbert Oosterwijk; Kirsten B Kluivers Journal: Int J Mol Sci Date: 2022-03-21 Impact factor: 5.923