Inhibition of Ninjurin 1 restores erectile function through dual angiogenic and neurotrophic effects in the diabetic mouse

Proceedings of the National Academy of Sciences of the United States of America

Volumn 111, Issue 26, 2014, Pages

  Yin, Guo Nan ^a   Choi, Min Ji ^a   Kim, Woo Jean ^a   Kwon, Mi Hye ^a   Song, Kang Moon ^a   Park, Jin Mi ^a   Das, Nando Dulal ^a   Kwon, Ki Dong ^a   Batbold, Dulguun ^a   Oh, Goo Taeg ^b   Koh, Gou Young ^c   Kim, Kyu Won ^d   Ryu, Ji Kan ^a   Suh, Jun Kyu ^a  

^a Inha University School of Medicine   (South Korea)

^b Ewha Womans University   (South Korea)

^c Korea Advanced Institute of Science and Technology (KAIST)   (South Korea)

^d Seoul National University   (South Korea)

Author keywords

Diabetes mellitus; Male sexual dysfunction; Peripheral neuropathy

Indexed keywords

ANGIOGENIC FACTOR; ANGIOPOIETIN 1; ANGIOPOIETIN 2; ANGIOPOIETIN RECEPTOR; CELL SURFACE PROTEIN; NERVE INJURY INDUCED PROTEIN 1; NEUROTROPHIC FACTOR; NEUTRALIZING ANTIBODY; SMALL INTERFERING RNA; STREPTOZOCIN; TRANSCRIPTOME; UNCLASSIFIED DRUG;

ANGIOGENESIS; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DIABETES MELLITUS; DOWN REGULATION; ERECTILE DYSFUNCTION; GENE EXPRESSION; MOUSE; NERVE REGENERATION; NONHUMAN; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; STREPTOZOTOCIN-INDUCED DIABETES MELLITUS;

DIABETES MELLITUS; MALE SEXUAL DYSFUNCTION; PERIPHERAL NEUROPATHY;

ANALYSIS OF VARIANCE; ANGIOPOIETIN-1; ANIMALS; ANTIBODIES, NEUTRALIZING; BLOTTING, WESTERN; CELL ADHESION MOLECULES, NEURONAL; DIABETES COMPLICATIONS; DNA PRIMERS; ERECTILE DYSFUNCTION; GENE EXPRESSION REGULATION; MALE; MICE; MICE, INBRED NOD; MICE, KNOCKOUT; NEOVASCULARIZATION, PHYSIOLOGIC; NERVE GROWTH FACTORS; NERVE REGENERATION; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; PENILE ERECTION; RECEPTOR, TIE-2; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION;

EID: 84903724128     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1403471111     Document Type: Article

References (31)

1. National Institutes of Health Consensus Development Panel on Impotence (1993) Impotence. NIH Consensus Conference. JAMA 270(1):83-90.
2. Friedewald VE, et al.; American Journal of Cardiology; Journal of Periodontology (2009) The American Journal of Cardiology and Journal of Periodontology Editors' Consensus: Periodontitis and atherosclerotic cardiovascular disease. Am J Cardiol 104(1):59-68.
3. Lue TF (2000) Erectile dysfunction. N Engl J Med 342(24):1802-1813.
4. Hakim LS, Goldstein I (1996) Diabetic sexual dysfunction. Endocrinol Metab Clin North Am 25(2):379-400.
5. Malavige LS, Levy JC (2009) Erectile dysfunction in diabetes mellitus. J Sex Med 6(5): 1232-1247.
6. Vignozzi L, et al. (2007) Testosterone regulates RhoA/Rho-kinase signaling in two distinct animal models of chemical diabetes. J Sex Med 4(3):620-630, discussion 631-632.
7. Martínez-Jabaloyas JM, et al. (2001) Prognostic factors for response to sildenafil in patients with erectile dysfunction. Eur Urol 40(6):641-646, discussion 647.
8. Musicki B, Burnett AL (2007) Endothelial dysfunction in diabetic erectile dysfunction. Int J Impot Res 19(2):129-138.
9. Angulo J, et al. (2010) Diabetes exacerbates the functional deficiency of NO/cGMP pathway associated with erectile dysfunction in human corpus cavernosum and penile arteries. J Sex Med 7(2 Pt 1):758-768.
10. Davis S, et al. (1996) Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning. Cell 87(7):1161-1169.
11. Ward NL, Dumont DJ (2002) The angiopoietins and Tie2/Tek: Adding to the complexity of cardiovascular development. Semin Cell Dev Biol 13(1):19-27.
12. Suri C, et al. (1996) Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell 87(7):1171-1180.
13. Kwon MH, et al. (2013) Effect of intracavernous administration of angiopoietin-4 on erectile function in the streptozotocin-induced diabetic mouse. J Sex Med 10(12): 2912-2927.
14. Jin HR, et al. (2011) Intracavernous delivery of a designed angiopoietin-1 variant rescues erectile function by enhancing endothelial regeneration in the streptozotocininduced diabetic mouse. Diabetes 60(3):969-980.
15. Jin HR, et al. (2010) Intracavernous delivery of synthetic angiopoietin-1 protein as a novel therapeutic strategy for erectile dysfunction in the type II diabetic db/db mouse. J Sex Med 7(11):3635-3646.
16. Bennett NE, et al. (2005) Improvement in erectile dysfunction after neurotrophic factor gene therapy in diabetic rats. J Urol 173(5):1820-1824.
17. Araki T, Milbrandt J (1996) Ninjurin, a novel adhesion molecule, is induced by nerve injury and promotes axonal growth. Neuron 17(2):353-361.
18. Ifergan I, et al. (2011) Role of Ninjurin-1 in the migration of myeloid cells to central nervous system inflammatory lesions. Ann Neurol 70(5):751-763.
19. Lee HJ, et al. (2009) Ninjurin1 mediates macrophage-induced programmed cell death during early ocular development. Cell Death Differ 16(10):1395-1407.
20. Jin HR, et al. (2009) Functional and morphologic characterizations of the diabetic mouse corpus cavernosum: Comparison of a multiple low-dose and a single high-dose streptozotocin protocols. J Sex Med 6(12):3289-3304.
21. Zhang LW, et al. (2008) Role of increased penile expression of transforming growth factor-beta1 and activation of the Smad signaling pathway in erectile dysfunction in streptozotocin-induced diabetic rats. J Sex Med 5(10):2318-2329.
22. Burchardt T, et al. (2000) Reduction of endothelial and smooth muscle density in the corpora cavernosa of the streptozotocin induced diabetic rat. J Urol 164(5): 1807-1811.
23. Augustin HG, Koh GY, Thurston G, Alitalo K (2009) Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system. Nat Rev Mol Cell Biol 10(3): 165-177.
24. Kim I, et al. (2000) Angiopoietin-1 regulates endothelial cell survival through the phosphatidylinositol 3'-Kinase/Akt signal transduction pathway. Circ Res 86(1):24-29.
25. Papapetropoulos A, et al. (2000) Angiopoietin-1 inhibits endothelial cell apoptosis via the Akt/survivin pathway. J Biol Chem 275(13):9102-9105.
26. Stone JR, Collins T (2002) The role of hydrogen peroxide in endothelial proliferative responses. Endothelium 9(4):231-238.
27. Łuczak K, Balcerczyk A, Soszynski M, Bartosz G (2004) Low concentration of oxidant and nitric oxide donors stimulate proliferation of human endothelial cells in vitro. Cell Biol Int 28(6):483-486.
28. Griendling KK, Sorescu D, Ushio-Fukai M (2000) NAD(P) H oxidase: Role in cardiovascular biology and disease. Circ Res 86(5):494-501.
29. Brüne B, et al. (2013) Redox control of inflammation in macrophages. Antioxid Redox Signal 19(6):595-637.
30. Hurt KJ, et al. (2002) Akt-dependent phosphorylation of endothelial nitric-oxide synthase mediates penile erection. Proc Natl Acad Sci USA 99(6):4061-4066.
31. Lee J, et al. (2013) Angiopoietin-1 guides directional angiogenesis through integrin alphavbeta5 signaling for recovery of ischemic retinopathy. Sci Transl Med 5(203): 203ra127.