Oxidative-stress-induced biosignatures: a predictor of allograft dysfunction?

• Published in: The Lancet (British edition) 2016-02, Vol.387, p.S100-S100
• Main Authors: Thompson, Emily, Dr, Brain, John G, PhD, Ali, Simi, Prof, Kirby, John A, Prof
• Format: Article
• Language: English
• Subjects: Hydrogen peroxide; Internal Medicine; Liver transplantation; Oxidative stress; Statistical analysis; Variance analysis
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(16)00487-6

Abstract Background Chronic graft dysfunction is the commonest cause of graft loss and is affected by perioperative factors. In liver transplantation, perioperative oxidative stress precipitates a senescence-associated secretory phenotype in biliary epithelial cells and this could be one of the factors responsible for fibrosis and allograft dysfunction. We aimed to examine effects of oxidative stress on biliary epithelial cells and assess the transcriptome of time-zero liver transplant biopsies for biomarkers of allograft dysfunction. Methods To model oxidative stress, the biliary epithelial cell H69 cell line was exposed to hydrogen peroxide in vitro. Immunofluorescence was performed post injury for protein expression associated with senescence and epithelial-mesenchymal transition. Similarly gene expression was analysed with both Taqman real-time PCR and a SYBR Green custom gene array (Thermo Fisher, Waltham, MA, USA). These experiments were repeated in triplicate. Similarly, the transcriptome of six time-zero liver transplant biopsy samples were analysed to examine in-vivo effects. A one-way ANOVA was performed for statistical analysis. Findings Oxidative stress induced gene expression upregulation of senescence marker p21 (p