Therapies for prostate cancer including radical surgery, radiation, and hormonal therapy are the leading cause of iatrogenic erectile dysfunction (ED). The cavernous nerve, the nerve that controls penile erection, is on the capsule of the prostate and is frequently injured during radical pelvic surgery for cancer of the prostate as well as bladder and rectum. Supported by NIH grant """"""""Treatment and prevention of impotence"""""""" , R01 DK45370, Jan 1/1998- 12/31/2001, we found that systemic growth hormone and insulin-like growth factor (IGF) enhanced regeneration of the cavernous nerves and recovery of erectile function. However, the recovery is partial in young rats and minimal in old rats. In addition, concerns have been expressed regarding using growth hormone or IGF in patients after cancer therapy. Therefore, we performed several preliminary studies on the effect of neurotrophin on cavernous nerve regeneration and obtained very exciting results. The goals of this proposed project are to explore the potential of vascular endothelial growth factor (VEGF) - enhanced brain derived neurotrophic factor (BDNF) therapy on cavernous nerve regeneration and recovery of erectile function. In addition, we have identified that among the signaling pathways, Jak/STAT pathway seems to be the main one associated with BDNF enhanced neurite growth. We therefore also propose to confirm this finding and identify the missing link between BDNF and Jak/STAT pathway. We will also study the phosphorylation cascades, cytokine and growth factor expression associated with cavernous nerve injury and BDNF-enhanced regeneration. This proposal is aiming at improving our understanding of the molecular mechanism of cavernous nerve injury and regeneration and translates the knowledge to clinical use. Successful completion of this project will not only significantly improve our understanding of the basic mechanism of cavernous nerve injury and regeneration but may also offer a """"""""cure"""""""" for neurogenic ED from various causes to tens of thousands of patients.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Method to Extend Research in Time (MERIT) Award (R37)
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Special Emphasis Panel (ZRG1-UROL (01))
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Rankin, Tracy L
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Lu, Zhihua; Lin, Guiting; Reed-Maldonado, Amanda et al. (2017) Low-intensity Extracorporeal Shock Wave Treatment Improves Erectile Function: A Systematic Review and Meta-analysis. Eur Urol 71:223-233
Lin, Guiting; Reed-Maldonado, Amanda B; Wang, Bohan et al. (2017) In Situ Activation of Penile Progenitor Cells With Low-Intensity Extracorporeal Shockwave Therapy. J Sex Med 14:493-501
Lin, Guiting; Zhang, Haiyang; Sun, Fionna et al. (2016) Brain-derived neurotrophic factor promotes nerve regeneration by activating the JAK/STAT pathway in Schwann cells. Transl Androl Urol 5:167-75
Lin, Guiting; Alwaal, Amjad; Zhang, Xiaoyu et al. (2015) Presence of stem/progenitor cells in the rat penis. Stem Cells Dev 24:264-70
Alwaal, Amjad; Hussein, Ahmed Aly; Zaid, Uwais B et al. (2015) Management of Peyronie's disease after collagenase (Xiaflex:®). Curr Drug Targets 16:484-94
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
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, Ching-Shwun; Lue, Tom F (2013) Adipose-derived stem cells for the treatment of Peyronie's disease? Eur Urol 63:561-2
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

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