title: Nerve injury-induced protein 1 (Ninjurin-1) is a novel therapeutic target for cavernous nerve injury-induced erectile dysfunction in mice.
abstract: BACKGROUND
  Radical prostatectomy for prostate cancer can not only induce cavernous nerve injury (CNI) but also result in structural changes in the cavernous tissues. Nerve injury-induced protein 1, Ninjurin-1 (Ninj1), is known to be involved in neuroinflammatory processes and to be related to vascular regression during the embryonic period.
  
  
  OBJECTIVE
  The study aims to determine whether and how Ninj1 neutralizing antibody (Ninj1-Ab) restores erectile function in mice with CNI.
  
  
  METHODS
  Twelve-week-old C57BL/6J mice were used and distributed into four groups: sham operation group and CNI groups receiving a single intracavernous injection of immunoglobulin G (IgG) control antibody, low-dose Ninj1-Ab (1.0 μg/20 μL), or high-dose Ninj1-Ab (2.5 μg/20 μL).
  
  
  METHODS
  One week after bilateral cavernous nerve crush, erectile function was measured by electrical stimulation of the cavernous nerve. The penis was harvested for histologic examinations and Western blot analysis.
  
  
  RESULTS
  The cavernous expression of Ninj1 protein was upregulated up to 7 days after CNI and returned to baseline levels thereafter. Local delivery of Ninj1-Ab significantly increased penile neuronal nitric oxide synthase and neurofilament contents, induced cavernous endothelial proliferation and phosphorylation of Akt and endothelial nitric oxide synthase, and decreased endothelial cell apoptosis in the CNI mice by upregulating angiopoietin-1 and downregulating angiopoietin-2. High-dose Ninj1-Ab induced profound restoration of erectile function in the CNI mice (91% of sham control values), whereas low-dose Ninj1-Ab elicited partial improvement.
  
  
  CONCLUSIONS
  The dual neurotrophic and angiogenic effects of Ninj1 blockade may provide a good opportunity for treating erectile dysfunction resulting from radical prostatectomy.
authors.affiliation: Department of Urology, National Research Center for Sexual Medicine, Inha University School of Medicine, Incheon, Korea.
authors.forename: Guo Nan
authors.initials: GN
authors.lastname: Yin
authors.forename: Woo Jean
authors.initials: WJ
authors.lastname: Kim
authors.forename: Hai-Rong
authors.initials: HR
authors.lastname: Jin
authors.forename: Mi-Hye
authors.initials: MH
authors.lastname: Kwon
authors.forename: Kang-Moon
authors.initials: KM
authors.lastname: Song
authors.forename: Min Ji
authors.initials: MJ
authors.lastname: Choi
authors.forename: Jin-Mi
authors.initials: JM
authors.lastname: Park
authors.forename: Nando Dulal
authors.initials: ND
authors.lastname: Das
authors.forename: Ki-Dong
authors.initials: KD
authors.lastname: Kwon
authors.forename: Dulguun
authors.initials: D
authors.lastname: Batbold
authors.forename: Kyu-Won
authors.initials: KW
authors.lastname: Kim
authors.forename: Ji-Kan
authors.initials: JK
authors.lastname: Ryu
authors.forename: Jun-Kyu
authors.initials: JK
authors.lastname: Suh
mesh_terms: D042683:Angiopoietin-1 / Q000378:metabolism; D042702:Angiopoietin-2 / Q000378:metabolism; D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000494:pharmacology*; D015816:Cell Adhesion Molecules, Neuronal / Q000037:antagonists & inhibitors* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004558:Electric Stimulation; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000378:metabolism; D005355:Fibrosis; D007267:Injections; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009409:Nerve Crush; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors* / Q000276:immunology; D009416:Nerve Regeneration / Q000187:drug effects; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010410:Penile Erection / Q000187:drug effects*; D010413:Penis / Q000187:drug effects* / Q000294:innervation / Q000473:pathology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; C467628:Angpt1 protein, mouse; D057134:Antibodies, Neutralizing; D015816:Cell Adhesion Molecules, Neuronal; D009414:Nerve Growth Factors; C484439:Ninj1 protein, mouse; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496321:Nos1 protein, mouse; C496315:Nos3 protein, mouse; D051057:Proto-Oncogene Proteins c-akt