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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 \u03b2-catenin expression was observed in the keloid region compared to the adjacent normal tissues. The activity of \u03b2-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, \u03b2-catenin, phosphorylated glycogen synthase kinase 3 beta, Smad 2\/3 complex, and TGF-\u03b21 were decreased in Wnt3a- or TGF-\u03b21-activated HDFs, following administration of dE1-k35\/sLRP6E1E2. Moreover, dE1-k35\/sLRP6E1E2 markedly inhibited nuclear translocation of both \u03b2-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.<\/jats:p>","DOI":"10.1038\/s41598-017-14893-w","type":"journal-article","created":{"date-parts":[[2017,11,2]],"date-time":"2017-11-02T21:55:26Z","timestamp":1509659726000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Decoy Wnt receptor (sLRP6E1E2)-expressing adenovirus induces anti-fibrotic effect via inhibition of Wnt and TGF-\u03b2 signaling"],"prefix":"10.1038","volume":"7","author":[{"given":"Won Jai","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Sun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo Min","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youjin","family":"Na","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8128-791X","authenticated-orcid":false,"given":"Chae Eun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju Hee","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JinWoo","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chae-Ok","family":"Yun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,11,8]]},"reference":[{"key":"14893_CR1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/S1357-4310(97)80541-2","volume":"4","author":"TL Tuan","year":"1998","unstructured":"Tuan, T. L. & Nichter, L. S. The molecular basis of keloid and hypertrophic scar formation. Molecular medicine today \n                           4, 19\u201324, https:\/\/doi.org\/10.1016\/s1357-4310(97)80541-2 (1998).","journal-title":"Molecular medicine today"},{"key":"14893_CR2","doi-asserted-by":"publisher","first-page":"150e","DOI":"10.1097\/01.prs.0000191977.51206.43","volume":"116","author":"A Burd","year":"2005","unstructured":"Burd, A. & Huang, L. Hypertrophic Response and Keloid Diathesis: Two Very Different Forms of Scar. Plastic and Reconstructive Surgery \n                           116, 150e\u2013157e, https:\/\/doi.org\/10.1097\/01.prs.0000191977.51206.43 (2005).","journal-title":"Plastic and Reconstructive Surgery"},{"key":"14893_CR3","doi-asserted-by":"publisher","first-page":"1435","DOI":"10.1097\/00006534-199910000-00031","volume":"104","author":"FB Niessen","year":"1999","unstructured":"Niessen, F. B., Spauwen, P. H., Schalkwijk, J. & Kon, M. 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