Regulatory effects of electronic beam irradiation on mir-21/smad7-mediated collagen I synthesis in keloid-derived fibroblasts.
Keloid scarring is an abnormal pathological scar characterized by excessive fibro proliferation and extracellular matrix deposition. Electronic beam irradiation is commonly used with surgical removal to control high recurrence rates of keloid scarring; however, the mechanism remains unknown. In this study, we used keloid-derived primary fibroblasts (KF) as the cell model, and a dose of 15 Gy energy, followed by quantitative PCR (qPCR), western blotting and gene overexpression/knock down techniques were used to reveal the molecular mechanisms affected by electronic beam irradiation. We found that mir-21 was highly expressed in KF and was downregulated by irradiation. We also showed that smad7 was a direct target of mir-21. Moreover, the expression level of smad7 was low in KF and upregulated by irradiation. We also found that smad7 controls Col-1 synthesis by mediating p38 phosphorylation, and this process was affected by electronic beam irradiation. The regulatory effect of electronic beam irradiation on the expression of mir-21, smad7, p38, p-p38 and Col-1 could be partly restored by mir-21 overexpression achieved by mir-21 mimic transfection. In conclusion, our data demonstrated that mir-21/smad7 regulated Col-1 expression in KF and that electronic beam irradiation was capable of decreasing Col-1 production by modifying mir-21/smad7-mediated p38 activation. This is the first report identifying the effects of electronic beam irradiation on miRNAs, providing a novel strategy to discover the molecular mechanisms of radiotherapy.
Department of Plastic and Aesthetic Surgery, Xiangya Hospital of Central South University, Changsha City, Hunan Province 410008, China.|Department of Plastic and Cosmetic Surgery, The first people's hospital of Chenzhou, Chenzhou City, Hunan Province 423000, China.
Shifeng
S
Li
Department of Pathology, The Affiliated Cancer Hospital of Xiangya Medical School, Changsha City, Hunan Province 410013, China.
Wei
W
Liu
Department of Plastic and Cosmetic Surgery, The people's hospital of Hunan province, Changsha City, Hunan Province 410000, China.
Ying
Y
Lei
Department of Plastic and Aesthetic Surgery, Xiangya Hospital of Central South University, Changsha City, Hunan Province 410008, China jianhonglong@126.com.
Jianhong
http://orcid.org/0000-0003-2325-2801
J
Long
Electronic beam irradiation; Keloid scarring; Radiotherapy; mir-21; p38 phosphorylation; smad7
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