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Title: Proteomic Profiling of Radiation-Induced Skin Fibrosis in Rats: Targeting the Ubiquitin-Proteasome System

Abstract

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-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: Ourmore » findings illustrate the molecular changes during radiation-induced skin fibrosis and suggest that targeting the ubiquitin-proteasome system would be an effective countermeasure.« less

Authors:
 [1];  [2];  [3]; ; ;  [1];  [4];  [5];  [6];  [1];  [1];  [2]
  1. School of Radiation Medicine and Protection and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou (China)
  2. (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)
Publication Date:
OSTI Identifier:
22648694
Resource Type:
Journal Article
Journal Name:
International Journal of Radiation Oncology, Biology and Physics
Additional Journal Information:
Journal Volume: 95; Journal Issue: 2; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0360-3016
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANIMAL TISSUES; ELECTRON BEAMS; FIBROSIS; FLUORINE COMPOUNDS; GROWTH FACTORS; GY RANGE 10-100; IN VITRO; IRRADIATION; RADIOTHERAPY; RATS; SKIN

Citation Formats

Wang, Wenjie, Cyrus Tang Hematology Center, Soochow University, Suzhou, Luo, Judong, Sheng, Wenjiong, Xue, Jiao, Li, Ming, Ji, Jiang, Liu, Pengfei, Zhang, Xueguang, Cao, Jianping, Zhang, Shuyu, E-mail: zhang.shuyu@hotmail.com, and Cyrus Tang Hematology Center, Soochow University, Suzhou. Proteomic Profiling of Radiation-Induced Skin Fibrosis in Rats: Targeting the Ubiquitin-Proteasome System. United States: N. p., 2016. Web. doi:10.1016/J.IJROBP.2016.01.021.
Wang, Wenjie, Cyrus Tang Hematology Center, Soochow University, Suzhou, Luo, Judong, Sheng, Wenjiong, Xue, Jiao, Li, Ming, Ji, Jiang, Liu, Pengfei, Zhang, Xueguang, Cao, Jianping, Zhang, Shuyu, E-mail: zhang.shuyu@hotmail.com, & Cyrus Tang Hematology Center, Soochow University, Suzhou. Proteomic Profiling of Radiation-Induced Skin Fibrosis in Rats: Targeting the Ubiquitin-Proteasome System. United States. doi:10.1016/J.IJROBP.2016.01.021.
Wang, Wenjie, Cyrus Tang Hematology Center, Soochow University, Suzhou, Luo, Judong, Sheng, Wenjiong, Xue, Jiao, Li, Ming, Ji, Jiang, Liu, Pengfei, Zhang, Xueguang, Cao, Jianping, Zhang, Shuyu, E-mail: zhang.shuyu@hotmail.com, and Cyrus Tang Hematology Center, Soochow University, Suzhou. Wed . "Proteomic Profiling of Radiation-Induced Skin Fibrosis in Rats: Targeting the Ubiquitin-Proteasome System". United States. doi:10.1016/J.IJROBP.2016.01.021.
@article{osti_22648694,
title = {Proteomic Profiling of Radiation-Induced Skin Fibrosis in Rats: Targeting the Ubiquitin-Proteasome System},
author = {Wang, Wenjie and Cyrus Tang Hematology Center, Soochow University, Suzhou and Luo, Judong and Sheng, Wenjiong and Xue, Jiao and Li, Ming and Ji, Jiang and Liu, Pengfei and Zhang, Xueguang and Cao, Jianping and Zhang, Shuyu, E-mail: zhang.shuyu@hotmail.com and Cyrus Tang Hematology Center, Soochow University, Suzhou},
abstractNote = {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-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.},
doi = {10.1016/J.IJROBP.2016.01.021},
journal = {International Journal of Radiation Oncology, Biology and Physics},
issn = {0360-3016},
number = 2,
volume = 95,
place = {United States},
year = {2016},
month = {6}
}