PMID- 32170840
OWN - NLM
STAT- MEDLINE
DCOM- 20210809
LR  - 20210809
IS  - 2047-2927 (Electronic)
IS  - 2047-2919 (Linking)
VI  - 8
IP  - 5
DP  - 2020 Sep
TI  - Intracavernous delivery of Dickkopf3 gene or peptide rescues erectile function 
      through enhanced cavernous angiogenesis in the diabetic mouse.
PG  - 1387-1397
LID - 10.1111/andr.12784 [doi]
AB  - BACKGROUND: Severe peripheral angiopathy in patients with diabetes is a major 
      contributing factor for low response rate to phosphodiesterase-5 inhibitors. 
      OBJECTIVES: 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. METHODS: 
      Eight-week-old C57BL/6 mice received intraperitoneal injections of streptozotocin 
      (50 mg/kg for 5 days). Eight weeks after the diabetes was induced, the efficacy 
      of DKK3 was determined by three independent experiments: experiment 1 (DKK3 
      peptide [5 mug in 20 muL PBS]); experiment 2 (DKK3 plasmid DNA with electroporation 
      [10, 40, or 100 mug in 20 muL PBS, respectively]); and experiment 3 (DKK3 
      adenovirus [1 x 10(7) , 1 x 10(8) , 1 x 10(9) virus particles per 20 muL, 
      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. RESULTS: 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-1, vascular endothelial growth 
      factor, and basic fibroblast growth factor) and accelerated tube formation in 
      MCECs cultivated under the high-glucose condition in vitro. CONCLUSION: 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.
CI  - (c) 2020 American Society of Andrology and European Academy of Andrology.
FAU - Song, Kang-Moon
AU  - Song KM
AD  - National Research Center for Sexual Medicine and Department of Urology, Inha 
      University School of Medicine, Incheon, Korea.
FAU - Kim, Woo-Jean
AU  - Kim WJ
AD  - National Research Center for Sexual Medicine and Department of Urology, Inha 
      University School of Medicine, Incheon, Korea.
AD  - Department of Anatomy, Kosin University College of Medicine, Busan, Korea.
FAU - Choi, Min-Ji
AU  - Choi MJ
AD  - National Research Center for Sexual Medicine and Department of Urology, Inha 
      University School of Medicine, Incheon, Korea.
FAU - Limanjaya, Anita
AU  - Limanjaya A
AD  - National Research Center for Sexual Medicine and Department of Urology, Inha 
      University School of Medicine, Incheon, Korea.
FAU - Ghatak, Kalyan
AU  - Ghatak K
AD  - National Research Center for Sexual Medicine and Department of Urology, Inha 
      University School of Medicine, Incheon, Korea.
FAU - Minh, Nguyen Nhat
AU  - Minh NN
AD  - National Research Center for Sexual Medicine and Department of Urology, Inha 
      University School of Medicine, Incheon, Korea.
FAU - Ock, Jiyeon
AU  - Ock J
AD  - National Research Center for Sexual Medicine and Department of Urology, Inha 
      University School of Medicine, Incheon, Korea.
FAU - Yin, Guo Nan
AU  - Yin GN
AD  - National Research Center for Sexual Medicine and Department of Urology, Inha 
      University School of Medicine, Incheon, Korea.
FAU - Hong, Soon-Sun
AU  - Hong SS
AD  - Department of Drug Development, Inha University School of Medicine, Incheon, 
      Korea.
FAU - Suh, Jun-Kyu
AU  - Suh JK
AD  - National Research Center for Sexual Medicine and Department of Urology, Inha 
      University School of Medicine, Incheon, Korea.
FAU - Ryu, Ji-Kan
AU  - Ryu JK
AUID- ORCID: 0000-0003-0025-6025
AD  - National Research Center for Sexual Medicine and Department of Urology, Inha 
      University School of Medicine, Incheon, Korea.
AD  - Department of Urology, Inha University Hospital, Incheon, Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200410
PL  - England
TA  - Andrology
JT  - Andrology
JID - 101585129
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Dkk3 protein, mouse)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/*metabolism
MH  - Animals
MH  - Diabetes Mellitus, Experimental/*complications
MH  - Erectile Dysfunction/*etiology/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neovascularization, Physiologic/*physiology
MH  - Penile Erection/physiology
OTO - NOTNLM
OT  - Dickkopf3
OT  - angiogenesis
OT  - diabetes mellitus
OT  - endothelial dysfunction
OT  - erectile dysfunction
EDAT- 2020/03/15 06:00
MHDA- 2021/08/10 06:00
CRDT- 2020/03/15 06:00
PHST- 2020/02/21 00:00 [received]
PHST- 2020/03/11 00:00 [accepted]
PHST- 2020/03/15 06:00 [pubmed]
PHST- 2021/08/10 06:00 [medline]
PHST- 2020/03/15 06:00 [entrez]
AID - 10.1111/andr.12784 [doi]
PST - ppublish
SO  - Andrology. 2020 Sep;8(5):1387-1397. doi: 10.1111/andr.12784. Epub 2020 Apr 10.