In the past 1 and 1/2 years, supported by grant 1 R55DK51374, we have modified and tested the feasibility of developing a reproducible rat model to study female stress urinary incontinence. We have studied the effect of pregnancy and delivery on the ultrastructure and function of the continence mechanism. We also modified our model by using pregnant rats and placed a intravaginal balloon under traction to direct the force to the levators and perineum to simulate the human situation. The information we have gained strongly support our opinion that the continence mechanism in the rats is similar to that of humans. We therefore propose to study the molecular mechanism involved in the pathogenesis of female stress urinary incontinence. We hypothesize that birth trauma, hormonal deficiency (menopause) and old age affect the gene and protein expression of several growth factors (IGF system, FGF, NGF, TGF, PDGF) and receptors (adrenergic, muscarinic and estrogen) which in turn change the structure and function of the continence mechanism. The hypothesis will be tested by completing the following specific aims: 1. To study and compare the functional, ultrastructural, cellular and molecular changes of the continence mechanism a). during pregnancy and after spontaneous delivery, b) after oxytocin-induced delivery and c) after delivery by cesarean section. 2. To examine the functional, ultrastructural, cellular and molecular changes of the continence mechanism after repeated birth trauma. 3. To examine the functional, ultrastructural, cellular and molecular changes of the continence mechanism after simulated birth trauma and bilateral ovariectomy. 4. To determine the functional, ultrastructural, cellular and molecular changes of the continence mechanism after combined simulated birth trauma, ovariectomy and aging.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK051374-05
Application #
6476234
Study Section
Special Emphasis Panel (ZRG4-UROL (01))
Program Officer
Nyberg, Leroy M
Project Start
1996-12-01
Project End
2002-11-30
Budget Start
2001-12-01
Budget End
2002-11-30
Support Year
5
Fiscal Year
2002
Total Cost
$272,282
Indirect Cost
Name
University of California San Francisco
Department
Urology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Zhang, Haiyang; Lin, Guiting; Qiu, Xuefeng et al. (2012) Label retaining and stem cell marker expression in the developing rat urinary bladder. Urology 79:746.e1-6
Lin, Guiting; Liu, Gang; Banie, Lia et al. (2011) Tissue distribution of mesenchymal stem cell marker Stro-1. Stem Cells Dev 20:1747-52
Lin, Ching-Shwun (2011) Stem cell therapy for the bladder--where do we stand? J Urol 185:779-80
Lin, Guiting; Fandel, Thomas M; Shindel, Alan W et al. (2011) Modulation of smooth muscle tonus in the lower urinary tract: interplay of myosin light-chain kinase (MLCK) and MLC phosphatase (MLCP). BJU Int 108:E66-70
Ning, Hongxiu; Lin, Guiting; Lue, Tom F et al. (2011) Mesenchymal stem cell marker Stro-1 is a 75 kd endothelial antigen. Biochem Biophys Res Commun 413:353-7
Lin, Guiting; Huang, Yun-Ching; Wang, Guifang et al. (2010) Prominent expression of phosphodiesterase 5 in striated muscle of the rat urethra and levator ani. J Urol 184:769-74
Ning, Hongxiu; Liu, Gang; Lin, Guiting et al. (2009) Identification of an aberrant cell line among human adipose tissue-derived stem cell isolates. Differentiation 77:172-80
Ning, Hongxiu; Liu, Gang; Lin, Guiting et al. (2009) Fibroblast growth factor 2 promotes endothelial differentiation of adipose tissue-derived stem cells. J Sex Med 6:967-979
Lin, Guiting; Huang, Yun-Ching; Shindel, Alan W et al. (2009) Labeling and tracking of mesenchymal stromal cells with EdU. Cytotherapy 11:864-73
Lin, Guiting; Shindel, Alan W; Banie, Lia et al. (2009) Molecular mechanisms related to parturition-induced stress urinary incontinence. Eur Urol 55:1213-22

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