Expression profile of the free radicals metabolism and antioxidant genes in chronic obstructive lung disease

Abstract

Chronic obstructive pulmonary disease (COPD) is a multifactorial heterogeneous chronic inflammatory disease of the respiratory system. Oxidative stress plays a central role in the pathophysiology of COPD. The goal of the study is the identification of new molecular markers of COPD based on the analysis of the expression profile of genes involved to oxidative stress response and antioxidant protection in peripheral blood mononuclear cells. Methods. To identify differential gene expression in COPD we performed expression profiling of 84 oxidative stress response and antioxidant protection genes in peripheral blood mononuclear cells samples from COPD (N=10 with frequent exacerbation emphysema and bronchitis phenotype, N=10 rare exacerbation emphysema phenotype and N=10 smoking controls). RNA was isolated from PBMCs, and gene expression was assessed using RT2 Profiler PCR Arrays « Human Oxidative Stress Plus PCR Array» (Qiagen). Results. Significant changes were revealed in the expression profile of several genes in frequent exacerbation emphysema and bronchitis phenotype COPD phenotype: decreased expression of BNIP3, GCLC, PRNP, TTN, HSP90AA1 gene; and increased expression of FTH1, PRDX3, SOD2 genes. In the group of COPD patients with rare exacerbation emphysema phenotype, an increase in the transcriptional activity of most genes that play a key role in the mechanisms of cell protection from free radical damage was found: FTH1, PRDX3, SOD2, PTGR1,GPX4, GSR, PTGS1, HSPA1A, NCF1 и NCF2, PRDX5, SIRT2, SQSTM1, SRXN1, TXNRD2, LHPP. We confirmed the assumption that the blood cell transcriptome reflects the pathogenesis and systemic nature of COPD and can be considered as a source of information for assessing the severity of the disease, monitoring the effectiveness of therapy, and searching for new non-invasive biomarkers of the disease and its various phenotypes.