Investigation of the role of the autophagic protein LC3B in the regulation of human airway epithelium cell differentiation in COPD using a biomimetic model

Shiue Luen Chen, Hsiao Chun Chou, Kuan Chen Lin, Jia Wei Yang, Ren Hao Xie, Chong You Chen, Xin Yi Liu, Johnson H.Y. Chung, Guan Yu Chen*

*此作品的通信作者

研究成果: Article同行評審

4 引文 斯高帕斯(Scopus)

摘要

Chronic obstructive pulmonary disease (COPD) is one of the most lethal chronic disease worldwide; however, the establishment of reliable in vitro models for exploring the biological mechanisms of COPD remains challenging. Here, we determined the differences in the expression and characteristics of the autophagic protein LC3B in normal and COPD human small airway epithelial cells and found that the nucleus of COPD cells obviously accumulated LC3B. We next established 3D human small airway tissues with distinct disease characteristics by regulating the biological microenvironment, extracellular matrix, and air-liquid interface culture methods. Using this biomimetic model, we found that LC3B affects the differentiation of COPD cells into basal, secretory, mucous, and ciliated cells. Moreover, although chloroquine and ivermectin effectively inhibited the expression of LC3B in the nucleus, chloroquine specifically maintained the performance of LC3B in cytoplasm, thereby contributing to the differentiation of ciliated cells and subsequent improvement in the beating functions of the cilia, whereas ivermectin only facilitated differentiation of goblet cells. We demonstrated that the autophagic mechanism of LC3B in the nucleus is one factor regulating the ciliary differentiation and function of COPD cells. Our innovative model can be used to further analyze the physiological mechanisms in the in vitro airway environment.

原文English
文章編號100182
頁(從 - 到)1-9
頁數9
期刊Materials Today Bio
13
DOIs
出版狀態Published - 1月 2022

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