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Dickkopf 2-Expressing Adenovirus Increases the Survival of Random-Pattern Flaps and Promotes Vasculogenesis in a Rat Model

 Se Woon Choi  ;  Yeo Reum Jeon  ;  Wooyeol Baek  ;  Chae-Ok Yun  ;  Tai Suk Roh  ;  Won Jai Lee 
 ANNALS OF PLASTIC SURGERY, Vol.84(5) : 588-594, 2020-05 
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Background: Dickkopf 2 (DKK2) has important roles in vertebrate development; it inhibits Wnt signaling-related processes, such as axial patterning, limb development, somitogenesis, and eye formation. However, DKK2 also acts as a Wnt signaling agonist. Dickkopf 2, induced during endothelial cell morphogenesis, promotes angiogenesis in cultured human endothelial cells. In this study, we explored the effect of DKK2-expressing adenovirus on random-pattern flaps using a rodent model. Methods: A DKK2-expressing (dE1-RGD/DKK2) adenovirus was generated and 20 Sprague-Dawley rats were randomly divided into 2 groups: a DKK2 group and a control group. Each group was intradermally injected with 1 × 10 plaque-forming units of DKK2-expressing adenovirus (DKK2 group) or control virus (control group) 48 hours before and immediately before surgery. Then, random-pattern dorsal cutaneous flaps of 3 × 9 cm were elevated. Flap survival rates and cutaneous blood flow were measured over time, and immunohistochemical staining was performed 10 days after surgery to detect CD31 and vascular endothelial growth factor (VEGF). Results: Immunofluorescence staining confirmed the expression of DKK2 in the DKK2 group. The flap survival rate was higher in the DKK2 group (80.0 ± 4.49%) than in the control group (57.5 ± 4.21%; P < 0.05). Blood flow to the most distal compartment was higher in the DKK2 group than the control group during the early postoperative period. Although vascular density was greater in the DKK2 group, there was no difference in the VEGF concentration between groups. Conclusions: The findings of the present study suggest that the DKK2-expressing adenovirus increases the survival of the random-pattern cutaneous flap independently of VEGF. The administration of the DKK2-expressing adenovirus into elevated skin flaps increased the number of capillaries and blood flow, thereby improving skin flap survival.
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1. College of Medicine (의과대학) > Dept. of Plastic and Reconstructive Surgery (성형외과학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Institute for Cancer Research (암연구소) > 1. Journal Papers
Yonsei Authors
Roh, Tai Suk(노태석) ORCID logo https://orcid.org/0000-0001-8681-159X
Yun, Chae Ok(윤채옥)
Lee, Won Jai(이원재) ORCID logo https://orcid.org/0000-0003-3056-0503
Jeon, Yeo Reum(전여름)
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