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Title: Bleomycin-induced epithelial–mesenchymal transition in sclerotic skin of mice: Possible role of oxidative stress in the pathogenesis

Epithelial–mesenchymal transition (EMT) derived myofibroblasts are partly responsible for the increased collagen synthesis and deposition that occur in tissue fibrosis; however EMT occurrence in skin fibrosis and its mechanism remain unknown. The aim of this study was to investigate whether epithelial cells undergo EMT and determine the role of oxidative stress in this process. BALB/c mice were subcutaneously injected with bleomycin (BLM) or phosphate buffer saline (PBS) into the shaved back daily for 2, 3, and 4 weeks. Skin collagen deposition was evaluated by histopathology and Western blotting. EMT characteristics in the skin were determined by histopathology and immunofluorescent staining for E-cadherin and vimentin, which were further evaluated by Western blotting and reverse transcriptase polymerase chain reaction (RT-PCR). To investigate the role of oxidative stress in EMT, the antioxidant N-acetylcysteine (NAC) was intraperitoneally (100 mg/kg body weight/day) injected daily for 3 weeks. The epithelial suprabasal cells were detached from the basement membrane zone (BMZ) in the sclerotic skin treated with BLM. Immunofluorescent staining indicated vimentin-positive epithelial cells frequently occurring in the thickened epidermis of BLM-treated mice. Western blotting and RT-PCR showed that the expression of E-cadherin was significantly decreased but that of vimentin significantly increased in the skin treated withmore » BLM. NAC attenuated BLM induced oxidative damage, changes in E-cadherin and vimentin expressions and collagen deposition in the sclerotic skin of mice. This study provides the first evidence that BLM induces the EMT of the epithelial cells superficial to the basement membrane zone in the skin fibrosis. Oxidative stress may contribute, at least in part, to BLM induced EMT and skin fibrosis in mice. - Highlights: • We provided the first evidence that EMT occurred in BLM-induced skin fibrosis. • Epithelial cells superficial to the BMZ underwent EMT in BLM-induced skin fibrosis. • NAC attenuated EMT induction in the process of BLM-induced skin fibrosis. • NAC didn't significantly inhibit TGF-β expression in BLM-induced skin fibrosis.« less
 [1] ;  [2] ;  [3] ; ; ;  [4] ;  [5] ;  [1] ;  [2]
  1. Institute of Dermatology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui 230022 (China)
  2. (China)
  3. Department of Emergency Medicine and Critical Care Medicine, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui 230022 (China)
  4. Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui 230032 (China)
  5. Department of Biochemistry and Physiology, Faculty of Health and Medical Sciences, University of Surrey (United Kingdom)
Publication Date:
OSTI Identifier:
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 277; Journal Issue: 3; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States