2. Academic Validation
  3. Identification of Nicotinic Acetylcholine Receptor for N-Acetylcysteine to Rescue Nicotine-induced Injury Using Beating Cilia in Primary Tissue Derived Airway Organoids

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

  • Adv Sci (Weinh). 2025 Jan;12(1):e2407054. doi: 10.1002/advs.202407054.
Yichao Zheng 1 2,  Qinyong Tian 3,  Haowei Yang 1,  Yongde Cai 4,  Jiaxin Zhang 4,  Yifen Wu 5,  Shuo Zhu 6,  Zuocheng Qiu 7,  Yimin Lin 3,  Jiangquan Hong 3,  Yi Zhang 3,  David Dockrell 8,  Shaohua Ma 1 2
Affiliations

Affiliations

  • 1 Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School (SIGS), Tsinghua University, Shenzhen, 518055, China.
  • 2 Precision Medicine and Healthcare Research Centre, Tsinghua-Berkeley Shenzhen Institute (TBSI), Tsinghua University, Shenzhen, 518055, China.
  • 3 Department of Cardiothoracic Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, China.
  • 4 Institute of Biopharmaceutical and Health Engineering, State Key Laboratory of Chemical Oncogenomics, Shenzhen International Graduate School, Tsinghua University, Shenzhen, 518055, China.
  • 5 Department of Internal Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, China.
  • 6 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.
  • 7 Guangdong Provincial Key Laboratory of Speed Capability Research, Jinan University, Guangzhou, 510632, China.
  • 8 Department of Respiratory Medicine and MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, EH16 4TJ, UK.
PMID: 39582278 DOI: 10.1002/advs.202407054
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.

Keywords

NAC; airway organoid; beating clia; nicotinic receptor.

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