| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Outline of Final Research Achievements |
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 fibrosis (CF), but their role in the regulation of pulmonary emphysema and dysfunction of βENaC-transgenic (Tg) mice, a murine model of COPD/CF, is unknown. DNA microarray analysis revealed that protease- and oxidative stress-dependent pathways are activated in the lung tissue of βENaC-Tg mice. Here, treatments of βENaC-Tg mice with a serine protease inhibitor ONO3403 and an antioxidant N-acetylcystein significantly improved pulmonary emphysema and dysfunction. Moreover, depletion of a murine endogenous antioxidant Vitamin C (VC), by genetic disruption of VC-synthesizing enzyme SMP30 in βENaC-Tg mice, increased inflammatory status in lung tissue and exaggerated pulmonary emphysema with a significant decrease in pulmonary function, possibly due to an increased oxidative stress.
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