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Inhibition of Wnt signaling pathway suppresses radiation-induced dermal fibrosis

 Dong Won Lee  ;  Won Jai Lee  ;  Jaeho Cho  ;  Chae-Ok Yun  ;  Hyun Roh  ;  Hsien Pin Chang  ;  Tai Suk Roh  ;  Ju Hee Lee  ;  Dae Hyun Lew 
 SCIENTIFIC REPORTS, Vol.10(1) : 13594, 2020-08 
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Progressive fibrosis of the dermal tissues is a challenging complication of radiotherapy whose underlying mechanism is not fully understood, and there are few available treatments. The canonical Wnt/β-catenin signaling pathway plays an important role in fibrosis as well as in the epithelial-to-mesenchymal transition (EMT). We investigated whether inhibition of Wnt/β-catenin signaling with sLRP6E1E2, a molecule that binds to extracellular Wnt ligands, ameliorated radiation-induced fibrosis both in vitro and in vivo. Radiation with a single dose of 2 Gy not only facilitated fibrosis in cultured human dermal fibroblasts via activation of the Wnt/β-catenin pathway but also initiated EMT in cultured keratinocytes, developing collagen-producing mesenchymal cells. sLRP6E1E2-expressing adenovirus treatment exerted anti-fibrotic activity in irradiated cultured dermal fibroblasts and keratinocytes. In a mouse model, a single fraction of 15 Gy was delivered to the dorsal skins of 36 mice randomized into three groups: those receiving PBS, those receiving control adenovirus, and those receiving decoy Wnt receptor-expressing adenovirus (dE1-k35/sLRP6E1E2). The mice were observed for 16 weeks, and excessive deposition of type I collagen was suppressed by sLRP6E1E2-expressing adenovirus treatment. These results demonstrate that the modulation of the Wnt/β-catenin pathway has the potential to decrease the severity of radiation-induced dermal fibrosis.
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1. College of Medicine (의과대학) > Dept. of Plastic and Reconstructive Surgery (성형외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Roh, Tai Suk(노태석) ORCID logo https://orcid.org/0000-0001-8681-159X
Lew, Dae Hyun(유대현)
Lee, Dong Won(이동원) ORCID logo https://orcid.org/0000-0003-0046-3139
Lee, Won Jai(이원재) ORCID logo https://orcid.org/0000-0003-3056-0503
Lee, Ju Hee(이주희) ORCID logo https://orcid.org/0000-0002-1739-5956
Cho, Jae Ho(조재호) ORCID logo https://orcid.org/0000-0001-9966-5157
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