慢性阻塞性肺病
根據世界衛生組織的數據，慢性阻塞性肺病（COPD）在2021年被列為全球第四大死因，對人類健康構成了重大威脅。這一不僅影響患者的生活品質，還對社會醫療資源造成了沉重負擔。因此，我們持續深入研究COPD對人體的影響及其發病機制，以進一步增進對這一疾病的理解。 為了更全面地應對這一挑戰，我們積極與醫院合作，收集台灣的病例資料，並致力於建立一個屬於台灣本土的臨床資料庫。這個資料庫將成為我們研究的核心基石，助力於精準醫療的發展，使我們能夠針對台灣患者的需求，尋找更精確的診斷與防治方向。透過這些努力，我們希望能夠改善病患的生活質量，降低COPD對社會健康的影響，並促進醫療界對此疾病的關注與研究。最終，我們期望能為所有COPD患者帶來更好的治療選擇，並實現健康生活的願景。
研究團隊
Particulate matter-related ITIH4 deficiency is associated with an emphysema phenotype of COPD through JNK-dependent and JNK-independent signalling
Sheng-Ming Wu, Kuan-Yuan Chen, Hsiao-Chi Chuang, Shu-Chuan Ho, Cheng-Wei Lin, Chia-Li Han, Wei-Lun Sun, Po-Hao Feng, Shiou-Fu Lin, Yueh-Hsi Chen, Tzu-Tao Chen, Chien-Hua Tseng, Wen-Te Liu, Kang-Yun Lee
Graphical Abstract
Ambient particulate matter exposure is implicated in decreased inter-α-trypsin inhibitor heavy chain 4 (ITIH4) levels and the development of emphysema in individuals with COPD. Acute exposure to particulate matter with aerodynamic diameter <2.5 µm (PM2.5) leads to a reduction in ITIH4 expression through oxidative-stress-mediated protein depletion, an effect that is more pronounced in individuals with COPD. Patients with COPD also have reduced ITIH4 expression at the mRNA level, which might be related to chronic exposure to PM2.5 and is not oxidative-stress-mediated (not shown in this model).
Significantly, ITIH4 demonstrates protective roles against PM2.5 and oxidative-stress-induced apoptosis in lung epithelial cells via the activation of caspase-3. Additionally, the extracellular ITIH4 protein effectively mitigates PM2.5- or oxidative-stress-induced apoptosis. Mechanistically, ITIH4 alleviates the activation of c-Jun N-terminal kinase (JNK) induced by oxidative stress and decreases the levels of β-catenin. In contrast, an ITIH4 deficiency intensified the impact of oxidative stress. The effects of increased reactive oxygen species (ROS) may inactivate β-catenin survival signalling in a JNK-independent pathway.