机构：[1]School of Radiation Medicine and Protection and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, China[2]Cyrus Tang Hematology Center, Soochow University, Suzhou, China[3]Department of Radiotherapy, Changzhou Tumor Hospital, Soochow University, Changzhou, China[4]Department of Dermatology, the Second Affiliated Hospital of Soochow University, Suzhou, China[5]Department of Gastroenterology, the Affiliated Jiangyin Hospital of Southeast University, Jiangyin, China[6]Institute of Medical Biotechnology and Jiangsu Stem Cell Key Laboratory, Medical College of Soochow University,Suzhou, China
Purpose: To investigate the molecular changes underlying the pathogenesis of radiation-induced skin fibrosis. 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-beta downstream signaling but not TGF-beta 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. (C) 2016 Elsevier Inc. All rights reserved.
基金：
Supported by the National Natural Science Foundation of China
(81522039, 81472920, and 31400720), the Suzhou Administration of
Science & Technology (SYS201416), the Changzhou Science &
Technology Program (CJ20140050 and CJ20150938), and the National
Defense Basic Scientific Research Program of China (B3820133001).
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2015]版：
大类|2 区医学
小类|2 区核医学3 区肿瘤学
最新[2023]版：
大类|1 区医学
小类|2 区肿瘤学2 区核医学
JCR分区：
出版当年[2014]版：
Q1ONCOLOGYQ1RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
最新[2023]版：
Q1ONCOLOGYQ1RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
第一作者机构：[1]School of Radiation Medicine and Protection and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, China[2]Cyrus Tang Hematology Center, Soochow University, Suzhou, China
共同第一作者：
通讯作者：
通讯机构：[*1]No. 199 Ren’ai Rd, Suzhou 215123, China.
推荐引用方式(GB/T 7714)：
Wenjie Wang,Judong Luo,Wenjiong Sheng,et al.Proteomic Profiling of Radiation-Induced Skin Fibrosis in Rats: Targeting the Ubiquitin-Proteasome System[J].INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS.2016,95(2):751-60.doi:10.1016/j.ijrobp.2016.01.021.
APA：
Wenjie Wang,Judong Luo,Wenjiong Sheng,Jiao Xue,Ming Li...&Shuyu Zhang.(2016).Proteomic Profiling of Radiation-Induced Skin Fibrosis in Rats: Targeting the Ubiquitin-Proteasome System.INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS,95,(2)
MLA：
Wenjie Wang,et al."Proteomic Profiling of Radiation-Induced Skin Fibrosis in Rats: Targeting the Ubiquitin-Proteasome System".INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 95..2(2016):751-60
医学