The long-term objective of this research proposal is to develop the best strategy for treating human erectile dysfunction by understanding the molecular mechanisms associated with this disease. The main goal of this project is to elucidate the molecular mechanisms of impotence associated with penile nerve injury and aging, using rats as an experimental animal model. The rational for this project is that penile nerve injury and aging may play an important role in impotence and therefore understanding of this process will help in treatment of this disease. This proposal is based on the hypothesis that penile nerve injury and aging associated impotence may be due to alteration in nonadrenergic noncholinergic vasodilator system, nitric oxide synthase, guanylate cyclase and cyclic GMP mediated mechanisms. This hypothesis will be achieved through pursuit of the following specific aims: 1) To investigate the role of penile neural injury and aging on nonadrengergic, noncholinergic vasodilator system which is associated with erectile dysfunction. This objective will be achieved by examining the neuroanatomy of penile nerves by NADPH diaphorase (nitric oxide synthase) using immunohistochemistry, light and electron microscopy. 2) To elucidate the molecular mechanisms associated with nerve injury and aging mediated impotence. This objective will be achieved by determining nitric oxide synthase activity (enzymatic assay), immunohistochemistry), nitric oxide gene expression (Northern blot, RNase protection assay), guanylate cyclase, and cyclic GMP. 3) To investigate the role of nerve growth factor in regeneration of nonadrenergic noncholinergic nerves after neurotomy. This objective will be achieved by denervating cavernous nerves and chronic administration of nerve growth factor by an implanted osmotic pump. The nerve regeneration process will be examined by nitric oxide synthase staining and light and electron microscopy. The accomplishment of these experiments will clearly elucidate the molecular mechanisms of impotence associated with penile nerve injury and aging. This proposal will also investigate the nerve growth factor in regeneration of cavernous nerves which might help in treatment of erectile dysfunction associated with nerve injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK045370-02
Application #
2144595
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1994-08-01
Project End
1996-07-31
Budget Start
1995-08-15
Budget End
1996-07-31
Support Year
2
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Urology
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Lin, Guiting; Alwaal, Amjad; Zhang, Xiaoyu et al. (2015) Presence of stem/progenitor cells in the rat penis. Stem Cells Dev 24:264-70
Ning, Hongxiu; Lei, Hong-En; Xu, Yong-De et al. (2014) Conversion of adipose-derived stem cells into natural killer-like cells with anti-tumor activities in nude mice. PLoS One 9:e106246
Lin, Ching-Shwun; Xin, Zhongcheng; Dai, Jican et al. (2013) Stem-cell therapy for erectile dysfunction. Expert Opin Biol Ther 13:1585-97
Lin, Ching-Shwun; Lue, Tom F (2013) Defining vascular stem cells. Stem Cells Dev 22:1018-26
Lin, Ching-Shwun; Albersen, Maarten; Xin, Zhongcheng et al. (2013) Phosphodiesterase-5 expression and function in the lower urinary tract: a critical review. Urology 81:480-7
Lin, Ching-Shwun; Xin, Zhong-Cheng; Dai, Jican et al. (2013) Commonly used mesenchymal stem cell markers and tracking labels: Limitations and challenges. Histol Histopathol 28:1109-16
Ning, H; Lin, G; Lue, T F et al. (2013) A coculture system of cavernous endothelial and smooth muscle cells. Int J Impot Res 25:63-8
Lin, C-S; Xin, Z; Namiki, M et al. (2013) Direct androgen regulation of PDE5 gene or the lack thereof. Int J Impot Res 25:81-5
Ning, Hongxiu; Albersen, Maarten; Lin, Guiting et al. (2013) Effects of EdU labeling on mesenchymal stem cells. Cytotherapy 15:57-63
Wu, Alex; Lue, Tom (2012) Editorial comment. Urology 80:1373-4

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