慢性阻塞性肺病
According to statistics from the World Health Organization, chronic obstructive pulmonary disease (COPD) was listed as the fourth leading cause of death worldwide in 2021, posing a significant threat to human health. We continue to conduct in-depth research on the impact of COPD on the human body and its pathogenesis to further enhance our understanding of this disease. Through active collaboration with hospitals to collect cases in Taiwan, we are working diligently to build a clinical database specific to Taiwan. This database will serve as the core foundation of our research, allowing us to focus on the development of precision medicine and find more accurate diagnostic and prevention methods for Taiwanese patients.
Research Team
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.