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- Title
Pericyte-Derived Dickkopf2 Regenerates Damaged Penile Neurovasculature Through an Angiopoietin-1-Tie2 Pathway.
- Authors
Guo Nan Yin; Hai-Rong Jin; Min-Ji Choi; Limanjaya, Anita; Ghatak, Kalyan; Nguyen Nhat Minh; Jiyeon Ock; Mi-Hye Kwon; Kang-Moon Song; Heon Joo Park; Ho Min Kim; Young-Guen Kwon; Ji-Kan Ryu; Jun-Kyu Suh
- Abstract
Penile erection requires well-coordinated interactions between vascular and nervous systems. Penile neurovascular dysfunction is a major cause of erectile dysfunction (ED) in patients with diabetes, which causes poor response to oral phosphodiesterase-5 inhibitors. Dickkopf2 (DKK2), a Wnt antagonist, is known to promote angiogenesis. Here, using DKK2-Tg mice or DKK2 protein administration, we demonstrate that the overexpression of DKK2 in diabetic mice enhances penile angiogenesis and neural regeneration and restores erectile function. Transcriptome analysis revealed that angiopoietin-1 and angiopoietin-2 are target genes for DKK2. Using an endothelial cell-pericyte coculture system and ex vivo neurite sprouting assay, we found that DKK2-mediated juxtacrine signaling in pericyte-endothelial cell interactions promotes angiogenesis and neural regeneration through an angiopoietin-1-Tie2 pathway, rescuing erectile function in diabetic mice. The dual angiogenic and neurotrophic effects of DKK2, especially as a therapeutic protein, will open new avenues to treating diabetic ED.
- Publication
Diabetes, 2018, Vol 67, Issue 6, p1149
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db17-0833