Decoy Wnt receptor (sLRP6E1E2)-expressing adenovirus induces antifibrotic effect via inhibition of Wnt and TGF-beta signaling
- Title
- Decoy Wnt receptor (sLRP6E1E2)-expressing adenovirus induces antifibrotic effect via inhibition of Wnt and TGF-beta signaling
- Author
- 윤채옥
- Keywords
- KELOID PATHOGENESIS; PULMONARY-FIBROSIS; SYSTEMIC-SCLEROSIS; HYPERTROPHIC SCARS; CATENIN; PATHWAY; CANCER; FIBROBLASTS; ACTIVATION; EXPRESSION
- Issue Date
- 2017-11
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- SCIENTIFIC REPORTS, v. 7, Article no. 15070
- 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 '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.
- URI
- https://www.nature.com/articles/s41598-017-14893-whttps://repository.hanyang.ac.kr/handle/20.500.11754/116228
- ISSN
- 2045-2322
- DOI
- 10.1038/s41598-017-14893-w
- Appears in Collections:
- COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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