{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:08:57Z","timestamp":1792598937999,"version":"4.5.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,12,19]],"date-time":"2017-12-19T00:00:00Z","timestamp":1513641600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,12,19]],"date-time":"2017-12-19T00:00:00Z","timestamp":1513641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Penile erection is a neurovascular event and neurologic or vascular disturbances are major causes of erectile dysfunction (ED). Radical prostatectomy for prostate cancer not only induces cavernous nerve injury (CNI) but also results in cavernous angiopathy, which is responsible for poor responsiveness to oral phosphodiesterase-5 inhibitors. Dickkopf2 (DKK2) is known as a Wnt signaling antagonist and is reported to promote mature and stable blood vessel formation. Here, we demonstrated in CNI mice that overexpression of DKK2 by administering DKK2 protein or by using DKK2-Tg mice successfully restored erectile function: this recovery was accompanied by enhanced neural regeneration through the secretion of neurotrophic factors, and restoration of cavernous endothelial cell and pericyte content. DKK2 protein also promoted neurite outgrowth in an <jats:italic>ex vivo<\/jats:italic> major pelvic ganglion culture experiment and enhanced tube formation in primary cultured mouse cavernous endothelial cells and pericytes co-culture system <jats:italic>in vitro<\/jats:italic>. In light of critical role of neuropathy and angiopathy in the pathogenesis of radical prostatectomy-induced ED, reprogramming of damaged erectile tissue toward neurovascular repair by use of a DKK2 therapeutic protein may represent viable treatment option for this condition.<\/jats:p>","DOI":"10.1038\/s41598-017-17862-5","type":"journal-article","created":{"date-parts":[[2017,12,13]],"date-time":"2017-12-13T12:18:16Z","timestamp":1513167496000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Dickkopf2 rescues erectile function by enhancing penile neurovascular regeneration in a mouse model of cavernous nerve injury"],"prefix":"10.1038","volume":"7","author":[{"given":"Kalyan","family":"Ghatak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo Nan","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Ji","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Limanjaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Nhat","family":"Minh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyeon","family":"Ock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang-Moon","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Hyuk","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Guen","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho Min","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Kan","family":"Ryu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Kyu","family":"Suh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,12,19]]},"reference":[{"key":"17862_CR1","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1124\/pr.111.004515","volume":"63","author":"KE Andersson","year":"2011","unstructured":"Andersson, K. E. Mechanisms of penile erection and basis for pharmacological treatment of erectile dysfunction. Pharmacol. Rev. \n                           63, 811\u2013859 (2011).","journal-title":"Pharmacol. Rev."},{"key":"17862_CR2","doi-asserted-by":"publisher","DOI":"10.1038\/srep10891","volume":"5","author":"GN Yin","year":"2015","unstructured":"Yin, G. N. et al. The pericyte as a cellular regulator of penile erection and a novel therapeutic target for erectile dysfunction. Sci. Rep. \n                           5, 10891 (2015).","journal-title":"Sci. Rep."},{"key":"17862_CR3","doi-asserted-by":"crossref","unstructured":"National Institutes of Health Consensus Conference. Impotence. NIH Consensus Development Panel on Impotence. 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A mouse model of cavernous nerve injury-induced erectile dysfunction: functional and morphological characterization of the corpus cavernosum. J. Sex. Med. \n                           7, 3351\u20133364 (2010).","journal-title":"J. Sex. Med."},{"key":"17862_CR11","doi-asserted-by":"publisher","first-page":"1286","DOI":"10.1345\/aph.1E487","volume":"39","author":"SM Setter","year":"2005","unstructured":"Setter, S. M., Iltz, J. L., Fincham, J. E., Campbell, R. K. & Baker, D. E. Phosphodiesterase 5 inhibitors for erectile dysfunction. Ann. Pharmacother. \n                           39, 1286\u20131295 (2005).","journal-title":"Ann. Pharmacother."},{"key":"17862_CR12","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1159\/000049850","volume":"40","author":"JM Martinez-Jabaloyas","year":"2001","unstructured":"Martinez-Jabaloyas, J. M. et al. Prognostic factors for response to sildenafil in patients with erectile dysfunction. Eur. 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The effect of vascular endothelial growth factor and adeno-associated virus mediated brain derived neurotrophic factor on neurogenic and vasculogenic erectile dysfunction induced by hyperlipidemia. J. Urol. \n                           169, 1577\u20131581 (2003).","journal-title":"J. Urol."},{"key":"17862_CR32","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1038\/ijir.2008.1","volume":"20","author":"JE Dall\u2019Era","year":"2008","unstructured":"Dall\u2019Era, J. E. et al. Vascular endothelial growth factor (VEGF) gene therapy using a nonviral gene delivery system improves erectile function in a diabetic rat model. Int. J. Impot. Res. \n                           20, 307\u2013314 (2008).","journal-title":"Int. J. Impot. Res."},{"key":"17862_CR33","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1161\/01.CIR.102.13.e98","volume":"102","author":"RJ Lee","year":"2000","unstructured":"Lee, R. J. et al. 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Circulation \n                           102, 98\u2013901 (2000).","journal-title":"Circulation"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-17862-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-17862-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-17862-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T16:53:04Z","timestamp":1671814384000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-17862-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,19]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["17862"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-17862-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12,19]]},"assertion":[{"value":"24 May 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 December 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 December 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"17819"}}