Pharmacological and genetic approaches determine protease and oxidative stress as exacerbating factors in a mouse model of obstructive lung diseases

3^rd International Conference on Chronic Obstructive Pulmonary Disease

July 11-12, 2016 Brisbane, Australia

Tsuyoshi Shuto

Kumamoto University, Japan

Scientific Tracks Abstracts: J Pulm Respir Med

Abstract :

Protease-antiprotease imbalance and oxidative stress are considered to be major pathophysiological hallmarks of severe lung diseases including chronic obstructive pulmonary disease (COPD) and cystic fi brosis (CF), but their role in the regulation of mucus obstructive phenotypes including pulmonary emphysema and dysfunction of �²ENaC-transgenic (Tg) mice, a murine model of COPD/CF, is unknown. Here, DNA microarray analysis revealed that protease and oxidative stress-dependent pathways are activated in the lung tissue of �²ENaC-Tg mice. Treatments of �²ENaC-Tg mice with a serine protease inhibitor ONO3403 and an antioxidant N-acetylcystein signifi cantly improved pulmonary emphysema and dysfunction. Moreover, depletion of a murine endogenous antioxidant vitamin C (VC), by genetic disruption of VC-synthesizing enzyme senescence marker protein-30 (SMP30) in �²ENaC-Tg mice, increased infl ammatory status in lung tissue and exaggerated pulmonary emphysema with a signifi cant decrease in pulmonary function, possibly due to an increased oxidative stress. Th us, our results defi ne protease and oxidative stress as factors that exacerbate mucus obstructive phenotypes of a mouse model of COPD/CF.

Biography :

Tsuyoshi Shuto has received his PhD degree from Kumamoto University, Kumamoto, Japan, in 2006. He has joined Kumamoto University in 2001 as a Research Associate and in 2006 as a Lecturer/Assistant Professor in the Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences of Kumamoto University, where he is currently an Associate Professor since 2013. During 1999 to 2001 he was at House Ear Institute, USA as a Research Associate. From 2004 to 2005, he was engaged as a Visiting Researcher at California Pacifi c Medical Center Research Institute, USA. He has published more than 75 papers in reputed journals.

Email: tshuto@gpo.kumamoto-u.ac.jp