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Metformin Alleviates Radiation-Induced Skin Fibrosis via the Downregulation of FOXO3
- Title
- Metformin Alleviates Radiation-Induced Skin Fibrosis via the Downregulation of FOXO3
- Authors
- Kim, Jin-Mo; Yoo, Hyun; Kim, Jee-Youn; Oh, Sang Ho; Kang, Jeong Wook; Yoo, Byung Rok; Han, Song Yee; Kim, Cha Soon; Choi, Won Hoon; Lee, Eun-Jung; Byeon, Hyeong Ju; Lee, Won Jai; Lee, Yun-Sil; Cho, Jaeho
- Ewha Authors
- 이윤실
- SCOPUS Author ID
- 이윤실
- Issue Date
- 2018
- Journal Title
- CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
- ISSN
- 1015-8987
1421-9778
- Citation
- CELLULAR PHYSIOLOGY AND BIOCHEMISTRY vol. 48, no. 3, pp. 959 - 970
- Keywords
- Radiation-induced skin fibrosis; Metformin; FOXO3; PIK3r1
- Publisher
- KARGER
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Background/Aims: Radiation-induced skin fibrosis is a common side effect of clinical radiotherapy. Our previous next-generation sequencing (NGS) study demonstrated the reduced expression of the regulatory a subunit of phosphatidylinositol 3-kinase (PIK3r1) in irradiated murine skin. Metformin has been reported to target the PIK3-FOXO3 pathway. In this study, we investigated the effects of metformin on radiation-induced skin fibrosis. Methods: Metformin was orally administered to irradiated mice. Skin fibrosis was analyzed by staining with H&E and Masson's trichrome stain. The levels of cytokines and chemokines associated with fibrosis were analyzed by immunohistochemistry and quantitative RT-PCR. The roles of PIK3r1 and FOXO3 in radiation-induced skin fibrosis were studied by overexpressing PIK3r1 and transfecting FOXO3 siRNA in NIH3T3 cells and mouse-derived dermal fibroblasts (MDF). Results: The oral administration of metformin significantly reduced radiation-induced skin thickening and collagen accumulation and significantly reduced the radiation-induced expression of FOXO3 in murine skin. Additionally, the overexpression of PIK3r1 reduced the radiation-induced expression of FOXO3, while FOXO3 silencing decreased the radiation induced expression of TGF beta in vitro. Conclusions: The results indicated that metformin suppresses radiation-induced skin injuries by modulating the expression of FOXO3 through PIK3r1. Collectively, the data obtained in this study suggested that metformin could be a potent therapeutic agent for alleviating radiation-induced skin fibrosis. (C) 2018 The Author(s) Published by S. Karger AG, Basel
- DOI
- 10.1159/000491964
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
- Files in This Item:
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