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. A dose of 15Gy energy was used on the cells, followed by quantitative PCR (Q-PCR), Western blotting and gene overexpression/knock down techniques 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 mimics transfection. In conclusion, our data demonstrated that mir-21/smad7 regulated Col-1 expression in KF and that electronic beam irradiation was capable of decreasingCol-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.
- Received March 30, 2016.
- Accepted September 2, 2016.
- © 2016. Published by The Company of Biologists Ltd
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.