Format

Send to

Choose Destination
Diabetes. 2018 Jun;67(6):1149-1161. doi: 10.2337/db17-0833. Epub 2018 Mar 20.

Pericyte-Derived Dickkopf2 Regenerates Damaged Penile Neurovasculature Through an Angiopoietin-1-Tie2 Pathway.

Author information

1
National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Republic of Korea.
2
Department of Urology, Yuhuangding Hospital, Yantai, Shandong Province, People's Republic of China.
3
Hypoxia-Related Disease Research Center, Inha University College of Medicine, Incheon, Republic of Korea.
4
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
5
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
6
National Research Center for Sexual Medicine and Department of Urology, Inha University School of Medicine, Incheon, Republic of Korea jksuh@inha.ac.kr rjk0929@inha.ac.kr.
7
Inha Research Institute for Medical Sciences, Inha University College of Medicine, Incheon, Republic of Korea.

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.

PMID:
29559443
DOI:
10.2337/db17-0833
[Indexed for MEDLINE]
Free full text

Publication type, MeSH terms, Substances

Publication type

MeSH terms

Substances

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center