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Decoy Wnt receptor (sLRP6E1E2)-expressing adenovirus induces anti-fibrotic effect via inhibition of Wnt and TGF-β signaling

Authors
 Won Jai Lee  ;  Jung-Sun Lee  ;  Hyo Min Ahn  ;  Youjin Na  ;  Chae Eun Yang  ;  Ju Hee Lee  ;  JinWoo Hong  ;  Chae-Ok Yun 
Citation
 Scientific Reports, Vol.7(1) : 15070, 2017 
Journal Title
 Scientific Reports 
Issue Date
2017
Abstract
Aberrant activation of the canonical Wingless type (Wnt) signaling pathway plays a key role in the development of hypertrophic scars and keloids, and this aberrant activation of Wnt pathway can be a potential target for the development of novel anti-fibrotic agents. In this study, we evaluated the anti-fibrotic potential of a soluble Wnt decoy receptor (sLRP6E1E2)-expressing non-replicating adenovirus (Ad; dE1-k35/sLRP6E1E2) on human dermal fibroblasts (HDFs), keloid fibroblasts (KFs), and keloid tissue explants. Higher Wnt3a and β-catenin expression was observed in the keloid region compared to the adjacent normal tissues. The activity of β-catenin and mRNA expression of type-I and -III collagen were significantly decreased following treatment with dE1-k35/sLRP6E1E2 in HDFs and KFs. The expression of LRP6, β-catenin, phosphorylated glycogen synthase kinase 3 beta, Smad 2/3 complex, and TGF-β1 were decreased in Wnt3a- or TGF-β1-activated HDFs, following administration of dE1-k35/sLRP6E1E2. Moreover, dE1-k35/sLRP6E1E2 markedly inhibited nuclear translocation of both β-catenin and Smad 2/3 complex. The expression levels of type-I and -III collagen, fibronectin, and elastin were also significantly reduced in keloid tissue explants after treatment with dE1-k35/sLRP6E1E2. These results indicate that Wnt decoy receptor-expressing Ad can degrade extracellular matrix in HDFs, KFs, and primary keloid tissue explants, and thus it may be beneficial for treatment of keloids.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/161567
DOI
10.1038/s41598-017-14893-w
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Plastic and Reconstructive Surgery (성형외과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실)
Yonsei Authors
양채은(Yang, Chae Eun)
이원재(Lee, Won Jai)
이주희(Lee, Ju Hee)
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