Amelioration of radiation-induced skin injury by adenovirus-mediated heme oxygenase-1 (HO-1) overexpression in rats

Shuyu Zhang,Pengfei Liu,Xueguang Zhang,Jundong Zhou,Wei-Qun Ding,Chuanjun Song,Xingjun Meng,Ling Xie,Jinchang Wu,Jianping Cao

doi:10.1186/1748-717x-7-4

Abstract

ObjectiveRadiation-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.MethodsA 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.ResultsSubcutaneous 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.ConclusionsThe 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.

Highlights

Radiotherapy offers valuable alternatives to primary surgical approaches for cancer patients
The present study provides evidences for the protective role of heme oxygenase-1 (HO-1) in alleviating radiation-induced skin damage in rats, which is helpful for the development of therapy for radiation-induced skin injury
The infection and expression of Ad-Heme oxygenase-1 (HO1)-enhanced green fluorescent protein (EGFP) after its subcutaneous administration To illustrate the therapeutic role of Heme oxygenases (HO)-1 in radiationinduced skin injury, a recombinant adenovirus (AdHO1-EGFP) and a control adenovirus (Ad-EGFP) were constructed (Figure 1A)

Summary

Introduction

Radiotherapy offers valuable alternatives to primary surgical approaches for cancer patients. The skin is not the primary target, it may be significantly injured and its function profoundly impaired during radiation therapy [3,4]. While increased efforts have led to new treatment schedules that are designed to During radiation exposure, skin tissue damage occurs instantaneously, mediated by a burst of free radicals. In response to ionizing radiation exposure, signal transduction pathways, transcription factors, DNA repair enzymes and antioxidant enzymes are activated. Many of these signaling and gene expression pathways are involved in intracellular metabolic redox reactions to buffer the ROS [8]. High-dose ionizing radiation culminates in cutaneous cell death and profound impairment of skin function [4]

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