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 α 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 PIK3rl and FOXO3 in radiation-induced skin fibrosis were studied by overexpressing PIK3rl 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 TGFβ 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.
| Original language | English |
|---|---|
| Pages (from-to) | 959-970 |
| Number of pages | 12 |
| Journal | Cellular Physiology and Biochemistry |
| Volume | 48 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2018 Aug 1 |
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All Science Journal Classification (ASJC) codes
- Physiology
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Metformin Alleviates Radiation-Induced Skin Fibrosis via the Downregulation of FOXO3. / 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.
In: Cellular Physiology and Biochemistry, Vol. 48, No. 3, 01.08.2018, p. 959-970.Research output: Contribution to journal › Article
TY - JOUR
T1 - Metformin Alleviates Radiation-Induced Skin Fibrosis via the Downregulation of FOXO3
AU - Kim, Jin Mo
AU - Yoo, Hyun
AU - Kim, Jee Youn
AU - Oh, Sang Ho
AU - Kang, Jeong Wook
AU - Yoo, Byung Rok
AU - Han, Song Yee
AU - Kim, Cha Soon
AU - Choi, Won Hoon
AU - Lee, Eun Jung
AU - Byeon, Hyeong Ju
AU - Lee, Won Jai
AU - Lee, Yun Sil
AU - Cho, Jaeho
PY - 2018/8/1
Y1 - 2018/8/1
N2 - 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 α 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 PIK3rl and FOXO3 in radiation-induced skin fibrosis were studied by overexpressing PIK3rl 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 TGFβ 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.
AB - 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 α 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 PIK3rl and FOXO3 in radiation-induced skin fibrosis were studied by overexpressing PIK3rl 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 TGFβ 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.
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U2 - 10.1159/000491964
DO - 10.1159/000491964
M3 - Article
C2 - 30036874
AN - SCOPUS:85052468800
VL - 48
SP - 959
EP - 970
JO - Cellular Physiology and Biochemistry
JF - Cellular Physiology and Biochemistry
SN - 1015-8987
IS - 3
ER -