35 THERAPEUTIC EFFECTS OF INSULIN-LIKE GROWTH FACTOR-1 ON STRESS URINARY INCONTINENCE IN RATS WITH SIMULATED CHILD BIRTH TRAUMA INJURY

Abstract

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Basic Research I1 Apr 201235 THERAPEUTIC EFFECTS OF INSULIN-LIKE GROWTH FACTOR-1 ON STRESS URINARY INCONTINENCE IN RATS WITH SIMULATED CHILD BIRTH TRAUMA INJURY Yasuhiro Sumino, Satoru Yoshikawa, Hiromitsu Mimata, and Naoki Yoshimura Yasuhiro SuminoYasuhiro Sumino Pittsburgh, PA More articles by this author , Satoru YoshikawaSatoru Yoshikawa Pittsburgh, PA More articles by this author , Hiromitsu MimataHiromitsu Mimata Oita, Japan More articles by this author , and Naoki YoshimuraNaoki Yoshimura Pittsburgh, PA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.078AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Insulin-like growth factor-1 (IGF-1) plays an important role in cell proliferation, survival and regeneration in various tissues. However, the therapeutic potential of IGF-1 for stress urinary incontinence (SUI) has not been explored. We examined the effect of IGF-1 in a rat model of SUI induced by stimulated birth trauma. METHODS Simulated birth trauma was induced by vaginal distension (VD) with an inflated balloon catheter for 4 hrs in the vagina of female SD rats. At 4, 7, 14 and 28 days after VD, (1) functional assessments were performed by measuring leak point pressure (LPP), urethral baseline pressure (UBP) and urethral responses during passive increment in intravesicular pressure and (2) the expression of IGF-1 and IGF-1 receptor (IGF1R) mRNA and protein in damaged tissues was examined by real-time RT-PCR and immunohistochemistry. Thereafter, human recombinant IGF-1 (hrIGF-1) (50 and 150μg/kg/day) or vehicle (saline) was continuously delivered from 1 day before VD using subcutaneous osmotic pumps. At 4 and 7 days after VD, the effect of IGF-1 treatment was examined by ELISA measurement of serum hrIGF-1, functional analyses (LPP, UBP and urethral response), and Western blotting analysis of Akt signal transduction pathways in urethral tissues. RESULTS After 4 and 7 days, VD rats had significantly reduced LPP, UBP and urethral responses, with a recovery to the normal level 14 and 28 days after VD. mRNA and protein levels of IGF-1 and IGF1R were significantly increased in the urethra and pudendal nerves 4 and 7 days after VD. IGF-1 treatment (50 and 150μg/kg/day) increased serum hrIGF-1 levels to 17.8±5.3 and 40.4±12.5 ng/ml, respectively. These IGF-1-treated groups showed significant improvement in LPP, UBP and urethral responses 4 and 7 days after VD (Figure). Moreover, phosphorylated Akt was highly expressed in the IGF-1-treated urethra. CONCLUSIONS IGF-1 treatment accelerates recovery from SUI induced by stimulated child birth trauma in rats, possibly through activation of the Akt signal transduction pathway, suggesting that IGF-1 has an important role in the recovery from childbirth-related SUI. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e14-e15 Peer Review Report Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yasuhiro Sumino Pittsburgh, PA More articles by this author Satoru Yoshikawa Pittsburgh, PA More articles by this author Hiromitsu Mimata Oita, Japan More articles by this author Naoki Yoshimura Pittsburgh, PA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...