- 作者：Wenjie Wang ; PhD&lowast ; ; &dagger ; ; Judong Luo ; MD ; PhD&Dagger ; ; Wenjiong Sheng ; MD&lowast ; ; Jiao Xue ; PhD&lowast ; ; Ming Li ; PhD&lowast ; ; Jiang Ji ; PhD§ ; ; Pengfei Liu ; MD‖ ; Xueguang Zhang ; PhD¶ ; ; Jianping Cao ; PhD&lowast ; ; Shuyu Zhang ; PhD&lowast ; ; &dagger ; ; zhang.shuyu@hotmail.com" class="auth_mail" title="E-mail the corresponding author
- 刊名：International Journal of Radiation Oncology*Biology*Physics
- 出版年：2016
- 出版时间：1 June 2016
- 年：2016
- 卷：95
- 期：2
- 页码：751-760
- 全文大小：2848 K
Methods and Materials
Rat skin was irradiated to 30 or 45 Gy with an electron beam. Protein expression in fibrotic rat skin and adjacent normal tissues was quantified by label-free protein quantitation. Human skin cells HaCaT and WS-1 were treated by x-ray irradiation, and the proteasome activity was determined with a fluorescent probe. The effect of proteasome inhibitors on Transforming growth factor Beta (TGF-B) signaling was measured by Western blot and immunofluorescence. The efficacy of bortezomib in wound healing of rat skin was assessed by the skin injury scale.
Results
We found that irradiation induced epidermal and dermal hyperplasia in rat and human skin. One hundred ninety-six preferentially expressed and 80 unique proteins in the irradiated fibrotic skin were identified. Through bioinformatic analysis, the ubiquitin-proteasome pathway showed a significant fold change and was investigated in greater detail. In vitro experiments demonstrated that irradiation resulted in a decline in the activity of the proteasome in human skin cells. The proteasome inhibitor bortezomib suppressed profibrotic TGF-β downstream signaling but not TGF-β secretion stimulated by irradiation in HaCaT and WS-1 cells. Moreover, bortezomib ameliorated radiation-induced skin injury and attenuated epidermal hyperplasia.
Conclusion
Our findings illustrate the molecular changes during radiation-induced skin fibrosis and suggest that targeting the ubiquitin-proteasome system would be an effective countermeasure.