{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T14:36:45Z","timestamp":1777387005630,"version":"3.51.4"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,4,10]],"date-time":"2020-04-10T00:00:00Z","timestamp":1586476800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002635","name":"Inha University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002635","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011512","name":"National Science Foundation, United Arab Emirates","doi-asserted-by":"publisher","award":["2019M3E5D1A02069621;"],"award-info":[{"award-number":["2019M3E5D1A02069621;"]}],"id":[{"id":"10.13039\/100011512","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Severe peripheral angiopathy in patients with diabetes is a major contributing factor for low response rate to phosphodiesterase\u20105 inhibitors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To examine whether and how Dickkopf3 (DKK3), a secreted modulator of the Wnt pathway that known to be involved in endothelial cell repair and vascular progenitor cell migration, restores erectile function in diabetic mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eight\u2010week\u2010old C57BL\/6 mice received intraperitoneal injections of streptozotocin (50\u00a0mg\/kg for 5\u00a0days). Eight weeks after the diabetes was induced, the efficacy of DKK3 was determined by three independent experiments: experiment 1 (DKK3 peptide [5\u00a0\u03bcg in 20\u00a0\u03bcL PBS]); experiment 2 (DKK3 plasmid DNA with electroporation [10, 40, or 100\u00a0\u03bcg in 20\u00a0\u03bcL PBS, respectively]); and experiment 3 (DKK3 adenovirus [1\u00a0\u00d7\u00a010<jats:sup>7<\/jats:sup>, 1\u00a0\u00d7\u00a010<jats:sup>8<\/jats:sup>, 1\u00a0\u00d7\u00a010<jats:sup>9<\/jats:sup> virus particles per 20\u00a0\u03bcL, respectively]). Erectile function was measured by electrical stimulation of the cavernous nerve one week (for peptide) or two weeks (for genes) after treatment. The angiogenic activity of DKK3 was determined in diabetic penis in vivo and in primary cultured mouse cavernous endothelial cells (MCECs) in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The cavernous expression of DKK3 protein was significantly lower in the diabetic mice than in controls. DKK3 peptide or adenovirus significantly improved erectile function in diabetic mice (70% of the control values). DKK3 adenovirus profoundly restored cavernous endothelial cell and pericyte contents and increased endothelial junction proteins in diabetic mice in vivo. DKK3 peptide induced upregulation of angiogenic factors (angiopoietin\u20101, vascular endothelial growth factor, and basic fibroblast growth factor) and accelerated tube formation in MCECs cultivated under the high\u2010glucose condition in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>DKK3 restored cavernous vascular integrity and improved erectile function in diabetic mice. Therapeutic cavernous angiogenesis by the use of DKK3 will be a promising therapeutic strategy to treat diabetic erectile dysfunction.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.12784","type":"journal-article","created":{"date-parts":[[2020,3,14]],"date-time":"2020-03-14T06:54:40Z","timestamp":1584168880000},"page":"1387-1397","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Intracavernous delivery of Dickkopf3 gene or peptide rescues erectile function through enhanced cavernous angiogenesis in the diabetic mouse"],"prefix":"10.1111","volume":"8","author":[{"given":"Kang\u2010Moon","family":"Song","sequence":"first","affiliation":[{"name":"National Research Center for Sexual Medicine and Department of Urology Inha University School of Medicine Incheon Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Woo\u2010Jean","family":"Kim","sequence":"additional","affiliation":[{"name":"National 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