| Summary: | 碩士 === 國立成功大學 === 生物化學暨分子生物學研究所 === 100 === Pulmonary emphysema, a major subtype of chronic obstructive pulmonary disease (COPD) predicted to become the third most common cause of death worldwide by 2020, is defined as the enlargement of alveolar airspace and the loss of lung elasticity. This disease is mostly caused by cigarette smoking. Despite being the main risk factor, only about 20% of cigarette smokers develop emphysema. There may be unidentified genes predisposing to cigarette smoke-induced emphysema. Prothymosin α (ProT) is an acidic nuclear protein associated with oxidative stress and immunomodulation. In our previous studies, we demonstrated that ProT homozygous transgenic mice exhibit a emphysema-like phenotype. We also detected ProT overexpression in lung epithelium from smokers with emphysema. In this study, we investigated whether ProT is involved in the pathogenesis of cigarette smoke extract (CSE)-induced emphysema. In the rat model, we showed that ProT and phosphorylated NF-κB were overexpressed in the emphysematous parts after induction with CSE. Phosphorylated NF-κB and MMP-12 were also overexpressed in ProT homozygous transgenic mice with emphysema. Furthermore, ProT heterozygous mice treated with CSE developed more severe emphysema as compared to CSE-treated wild-type mice. Phosphorylated NF-κB and MMP-12 were overexpressed in the ProT transgenic mice after treatment with CSE. By contrast, CSE-induced emphysema could be prevented by inhibition of ProT expression. Phosphorylated NF-κB and MMP-12 were downregulated in the ProT knockdown mice. In addition, ProT-induced emphysema could also be prevented in MMP-12 knockout mice. Our in vitro study also showed that expressions of ProT and phosphorylated NF-κB were upregulated in A549 cells after treatment with CSE. Taken together, our studies demonstrate that ProT plays an important role in CSE-induced emphysema through upregulation of phosphorylated NF-κB and MMP-12.
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