title: Amelioration of radiation-induced skin injury by adenovirus-mediated heme oxygenase-1 (HO-1) overexpression in rats.
abstract: OBJECTIVE
  Radiation-induced skin injury remains a serious concern for radiation therapy. Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme catabolism, has been reported to have potential antioxidant and anti-apoptotic properties. However, the role of HO-1 in radiation-induced skin damage remains unclear. This study aims to elucidate the effects of HO-1 on radiation-induced skin injury in rats.
  
  
  METHODS
  A control adenovirus (Ad-EGFP) and a recombinant adenovirus (Ad-HO1-EGFP) were constructed. Rats were irradiated to the buttock skin with a single dose of 45 Gy followed by a subcutaneous injection of PBS, 5 × 109 genomic copies of Ad-EGFP or Ad-HO1-EGFP (n = 8). After treatment, the skin MDA concentration, SOD activity and apoptosis were measured. The expression of antioxidant and pro-apoptotic genes was determined by RT-PCR and real-time PCR. Skin reactions were measured at regular intervals using the semi-quantitative skin injury score.
  
  
  RESULTS
  Subcutaneous injection of Ad-HO1-EGFP infected both epidermal and dermal cells and could spread to the surrounding regions. Radiation exposure upregulated the transcription of the antioxidant enzyme genes, including SOD-1, GPx2 and endogenous HO-1. HO-1 overexpression decreased lipid peroxidation and inhibited the induction of ROS scavenging proteins. Moreover, HO-1 exerted an anti-apoptotic effect by suppressing FAS and FASL expression. Subcutaneous injection of Ad-HO1-EGFP demonstrated significant improvement in radiation-induced skin injury.
  
  
  CONCLUSIONS
  The present study provides evidences for the protective role of HO-1 in alleviating radiation-induced skin damage in rats, which is helpful for the development of therapy for radiation-induced skin injury.
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, China.
authors.forename: Shuyu
authors.initials: S
authors.lastname: Zhang
authors.forename: Chuanjun
authors.initials: C
authors.lastname: Song
authors.forename: Jundong
authors.initials: J
authors.lastname: Zhou
authors.forename: Ling
authors.initials: L
authors.lastname: Xie
authors.forename: Xingjun
authors.initials: X
authors.lastname: Meng
authors.forename: Pengfei
authors.initials: P
authors.lastname: Liu
authors.forename: Jianping
authors.initials: J
authors.lastname: Cao
authors.forename: Xueguang
authors.initials: X
authors.lastname: Zhang
authors.forename: Wei-Qun
authors.initials: WQ
authors.lastname: Ding
authors.forename: Jinchang
authors.initials: J
authors.lastname: Wu
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002478:Cells, Cultured; D005720:Gamma Rays / Q000009:adverse effects*; D051547:Heme Oxygenase-1 / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007668:Kidney / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D011832:Radiation Injuries / Q000201:enzymology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000201:enzymology / Q000293:injuries* / Q000528:radiation effects*
chemical_list: D012333:RNA, Messenger; D008315:Malondialdehyde; D051547:Heme Oxygenase-1