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

doi:10.1016/j.mtbio.2021.100182

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

Mater Today Bio. 2021 Dec 8:13:100182. doi: 10.1016/j.mtbio.2021.100182. eCollection 2022 Jan.

Authors

Shiue-Luen Chen^{1

2}, Hsiao-Chun Chou², Kuan-Chen Lin^{2

3}, Jia-Wei Yang^{1

2}, Ren-Hao Xie^{1

2}, Chong-You Chen^{1

2}, Xin-Yi Liu², Johnson H Y Chung⁴, Guan-Yu Chen^{1

2

5}

Affiliations

¹ Department of Electrical and Computer Engineering, College of Electrical and Computer Engineering, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
² Institute of Biomedical Engineering, College of Electrical and Computer Engineering, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
³ Division of Haematology/Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital (Linkou), Taoyuan, Taiwan.
⁴ ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, University of Wollongong, Wollongong, NSW, Australia.
⁵ Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.

Abstract

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.

Keywords: Airway epithelial cells; Autophagy; Cell differentiation; Chronic obstructive pulmonary disease; Cilia beating.