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

Won Jai Lee, Jung Sun Lee, Hyo Min Ahn, Youjin Na, Chae Eun Yang, Ju Hee Lee, Jinwoo Hong, Chae Ok Yun

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6 Citations (Scopus)


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.

Original languageEnglish
Article number15070
JournalScientific reports
Issue number1
Publication statusPublished - 2017 Dec 1

Bibliographical note

Funding Information:
This work was supported by grants from the Korea Science and Engineering Foundation (2015R1A2A1A13027811 and 2016M3A9B5942352; Dr. C-O. Yun), the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (2012-0008180 and 2014051295, WJ Lee). Co-supported by the Global High-tech Biomedicine Technology Development Program of the National Research Foundation (NRF) & Korea Health Industry Development Institute (KHIDI) funded by the Korean government (MSIP&MOHW) (2015M3D6A1065663).

Publisher Copyright:
© 2017 The Author(s).

All Science Journal Classification (ASJC) codes

  • General


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