Nicotinic Receptor Subunits Atlas in the Adult Human Lung

Abstract

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels responsible for rapid neural and neuromuscular signal transmission. Although it is well documented that 16 subunits are encoded by the human genome, their presence in airway epithelial cells (AECs) remains poorly understood, and contribution to pathology is mainly discussed in the context of cancer. We analysed nAChR subunit expression in the human lungs of smokers and non-smokers using transcriptomic data for whole-lung tissues, isolated large AECs, and isolated small AECs. We identified differential expressions of nAChRs in terms of detection and repartition in the three modalities. Smoking-associated alterations were also unveiled. Then, we identified an nAChR transcriptomic print at the single-cell level. Finally, we reported the localizations of detectable nAChRs in bronchi and large bronchioles. Thus, we compiled the first complete atlas of pulmonary nAChR subunits to open new avenues to further unravel the involvement of these receptors in lung homeostasis and respiratory diseases.

Lower Gene Expression of Angiotensin Converting Enzyme 2 Receptor in Lung Tissues of Smokers with COVID-19 Pneumonia

“…Indeed, nicotine has been shown to induce airway epithelial expression of the α7 subtype of nicotine acetylcholine receptors (α7-nAChR), which activates MAPK/ERK, resulting in ACE-2 overexpression in the same cells [22,25,[61][62][63]. Even if the precise nAChR subunit identification is difficult, others have also been reported associated to smoking (i.e., α5, α10, β2 and β3) [64] and some of them also involved in inflammatory process of lung tissues. Moreover, nicotine increases SARS-CoV-2 replication, transcription of viral proteins, and cytopathic effects [22,62].…”

An innate contribution of human nicotinic receptor polymorphisms to COPD-like lesions

“…This subunit is expressed by basal cells in the epithelium 23 , 25 , which are considered to act as progenitor cells 26 , 27 . In addition, we reported the expression and the localization of the α5 subunit in airway epithelial cells from bronchi and bronchioles in non-smokers 28 .…”

Chr15q25 Genetic Variant rs16969968 Alters Cell Differentiation in Respiratory Epithelia

“…We first confirmed the detection of CHRNA5 expression in bronchial epithelial cells using in situ hybridisation on formalin-fixed paraffin-embedded (FFPE) lung tissues (Supplemental Figure S1) [22]. We next compared epithelial remodelling features on lung tissues obtained from α5WT and α5SNP patients.…”