Inhibition of Wnt signaling pathway suppresses radiation-induced dermal fibrosis

Abstract 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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bf3f13052af349e892ead6c07108c6c5
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spelling	oai:doaj.org-article:bf3f13052af349e892ead6c07108c6c52021-12-02T16:43:42ZInhibition of Wnt signaling pathway suppresses radiation-induced dermal fibrosis10.1038/s41598-020-70243-32045-2322https://doaj.org/article/bf3f13052af349e892ead6c07108c6c52020-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-70243-3https://doaj.org/toc/2045-2322Abstract 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.Dong Won LeeWon Jai LeeJaeho ChoChae-Ok YunHyun RohHsien Pin ChangTai Suk RohJu Hee LeeDae Hyun LewNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 Inhibition of Wnt signaling pathway suppresses radiation-induced dermal fibrosis
description	Abstract 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.
format	article
author	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
author_facet	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
author_sort	Dong Won Lee
title	Inhibition of Wnt signaling pathway suppresses radiation-induced dermal fibrosis
title_short	Inhibition of Wnt signaling pathway suppresses radiation-induced dermal fibrosis
title_full	Inhibition of Wnt signaling pathway suppresses radiation-induced dermal fibrosis
title_fullStr	Inhibition of Wnt signaling pathway suppresses radiation-induced dermal fibrosis
title_full_unstemmed	Inhibition of Wnt signaling pathway suppresses radiation-induced dermal fibrosis
title_sort	inhibition of wnt signaling pathway suppresses radiation-induced dermal fibrosis
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/bf3f13052af349e892ead6c07108c6c5
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Inhibition of Wnt signaling pathway suppresses radiation-induced dermal fibrosis

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