Dickkopf2 rescues erectile function by enhancing penile neurovascular regeneration in a mouse model of cavernous nerve injury

Abstract 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 res...

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Autores principales:	Kalyan Ghatak, Guo Nan Yin, Min-Ji Choi, Anita Limanjaya, Nguyen Nhat Minh, Jiyeon Ock, Kang-Moon Song, Dong Hyuk Kang, Young-Guen Kwon, Ho Min Kim, Ji-Kan Ryu, Jun-Kyu Suh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cc590f5ccfc24d2c9e0c282f01ba65f2
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spelling	oai:doaj.org-article:cc590f5ccfc24d2c9e0c282f01ba65f22021-12-02T15:04:59ZDickkopf2 rescues erectile function by enhancing penile neurovascular regeneration in a mouse model of cavernous nerve injury10.1038/s41598-017-17862-52045-2322https://doaj.org/article/cc590f5ccfc24d2c9e0c282f01ba65f22017-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-17862-5https://doaj.org/toc/2045-2322Abstract 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 ex vivo major pelvic ganglion culture experiment and enhanced tube formation in primary cultured mouse cavernous endothelial cells and pericytes co-culture system in vitro. 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.Kalyan GhatakGuo Nan YinMin-Ji ChoiAnita LimanjayaNguyen Nhat MinhJiyeon OckKang-Moon SongDong Hyuk KangYoung-Guen KwonHo Min KimJi-Kan RyuJun-Kyu SuhNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kalyan Ghatak Guo Nan Yin Min-Ji Choi Anita Limanjaya Nguyen Nhat Minh Jiyeon Ock Kang-Moon Song Dong Hyuk Kang Young-Guen Kwon Ho Min Kim Ji-Kan Ryu Jun-Kyu Suh Dickkopf2 rescues erectile function by enhancing penile neurovascular regeneration in a mouse model of cavernous nerve injury
description	Abstract 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 ex vivo major pelvic ganglion culture experiment and enhanced tube formation in primary cultured mouse cavernous endothelial cells and pericytes co-culture system in vitro. 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.
format	article
author	Kalyan Ghatak Guo Nan Yin Min-Ji Choi Anita Limanjaya Nguyen Nhat Minh Jiyeon Ock Kang-Moon Song Dong Hyuk Kang Young-Guen Kwon Ho Min Kim Ji-Kan Ryu Jun-Kyu Suh
author_facet	Kalyan Ghatak Guo Nan Yin Min-Ji Choi Anita Limanjaya Nguyen Nhat Minh Jiyeon Ock Kang-Moon Song Dong Hyuk Kang Young-Guen Kwon Ho Min Kim Ji-Kan Ryu Jun-Kyu Suh
author_sort	Kalyan Ghatak
title	Dickkopf2 rescues erectile function by enhancing penile neurovascular regeneration in a mouse model of cavernous nerve injury
title_short	Dickkopf2 rescues erectile function by enhancing penile neurovascular regeneration in a mouse model of cavernous nerve injury
title_full	Dickkopf2 rescues erectile function by enhancing penile neurovascular regeneration in a mouse model of cavernous nerve injury
title_fullStr	Dickkopf2 rescues erectile function by enhancing penile neurovascular regeneration in a mouse model of cavernous nerve injury
title_full_unstemmed	Dickkopf2 rescues erectile function by enhancing penile neurovascular regeneration in a mouse model of cavernous nerve injury
title_sort	dickkopf2 rescues erectile function by enhancing penile neurovascular regeneration in a mouse model of cavernous nerve injury
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/cc590f5ccfc24d2c9e0c282f01ba65f2
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Dickkopf2 rescues erectile function by enhancing penile neurovascular regeneration in a mouse model of cavernous nerve injury

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