Journal
SCIENTIFIC REPORTS
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-017-14893-w
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Funding
- Korea Science and Engineering Foundation [2015R1A2A1A13027811, 2016M3A9B5942352]
- National Research Foundation of Korea (NRF) - Korea government (MEST) [2012-0008180, 2014051295]
- National Research Foundation (NRF) & Korea Health Industry Development Institute (KHIDI) - Korean government (MSIPMOHW) [2015M3D6A1065663]
- National Research Foundation of Korea [2015M3D6A1065663] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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 'beta-catenin expression was observed in the keloid region compared to the adjacent normal tissues. The activity of beta-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, beta-catenin, phosphorylated glycogen synthase kinase 3 beta, Smad 2/3 complex, and TGF-beta 1 were decreased in Wnt3a- or TGF-beta 1-activated HDFs, following administration of dE1-k35/sLRP6E1E2. Moreover, dE1-k35/sLRP6E1E2 markedly inhibited nuclear translocation of both beta-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.
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