journal article·2025-01Open access

Identification of Nicotinic Acetylcholine Receptor for N‐Acetylcysteine to Rescue Nicotine‐induced Injury Using Beating Cilia in Primary Tissue Derived Airway Organoids

Yichao Zheng, Qinyong Tian, Haowei Yang, Yongde Cai, Jiaxin Zhang, Yifen Wu, Shuo Zhu, Zuocheng Qiu, Yimin Lin, Jiangquan Hong, Yi Zhang, David Dockrell, Shaohua Ma

Advanced Science· Volume 12· Issue 1

Abstract

Abstract Smoking is one of the major contributors to airway injuries. N‐acetylcysteine (NAC) has been proposed as a treatment or preventive measure for such injuries. However, the exact nature of the smoking‐induced injury and the protective mechanism of NAC are not yet fully understood. Here, patient tissue‐derived airway organoids for modeling smoking‐induced injury, therapeutic investigation, and mechanism studies are developed. Airway organoids consist mainly of ciliated cells, together with basal cells, goblet cells, and myofibroblast‐like cells. The organoids display apical‐out and basal‐in polarity and are enriched in beating cilia, which are sensitive to smoking challenge and NAC treatment. An algorithm is developed to measure ciliary beating activity by analyzing the altered beating pattern of cilia in response to nicotine challenge and NAC treatment. Nicotinic acetylcholine receptors (nAChRs) expressed by airway organoids are involved in the mechanisms of nicotine‐induced injury through the nicotine‐nAChR pathway. In contrast to the common understanding that NAC has an antioxidative effect that mitigates airway damage, it is elucidated that NAC binding to nicotine can abolish the binding capacity of nicotine to nAChRs and thus prevent nicotine‐induced injury. This study focuses on the advances and potential of humanized organoids in understanding biological processes, mechanisms, and identifying therapeutic targets.
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Research context

OpenAlex topics: Nicotinic Acetylcholine Receptors Study · Ion channel regulation and function · Photoreceptor and optogenetics research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Institute of Biopharmaceutical and Health Engineering Tsinghua Shenzhen International Graduate School (SIGS) Tsinghua University Shenzhen 518055 China

Precision Medicine and Healthcare Research Centre Tsinghua‐Berkeley Shenzhen Institute (TBSI) Tsinghua University Shenzhen 518055 China

Department of Cardiothoracic Surgery Zhangzhou Affiliated Hospital of Fujian Medical University Zhangzhou 363000 China

Institute of Biopharmaceutical and Health Engineering State Key Laboratory of Chemical Oncogenomics Shenzhen International Graduate School Tsinghua University Shenzhen 518055 China

Department of Internal Medicine Zhangzhou Affiliated Hospital of Fujian Medical University Zhangzhou 363000 China

Key Laboratory of Rubber‐Plastics Ministry of Education/Shandong Provincial Key Laboratory of Rubber and Plastics Qingdao University of Science and Technology Qingdao 266042 China

Guangdong Provincial Key Laboratory of Speed Capability Research Jinan University Guangzhou 510632 China

Department of Respiratory Medicine and MRC Centre for Inflammation Research University of Edinburgh Edinburgh EH16 4TJ UK

Funding

Guangdong Provincial Department of Science and Technology · National Natural Science Foundation of China · Natural Science Foundation of Guangdong Province · Science, Technology and Innovation Commission of Shenzhen Municipality

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