Research progress on ciliated cells and pulmonary diseases: from basic science to clinical applications

doi:10.12092/j.issn.1009-2501.2026.07.016

Abstract

Abstract:

Ciliated cells, as crucial structural and functional units in pulmonary tissue, are predominantly distributed in airway epithelium. They participate in maintaining normal respiratory system functions through their unique ultrastructure and play pivotal roles in preserving airway immune homeostasis and regulating local immune responses. Recent advancements in ciliated cell research have progressively elucidated their developmental processes, physiological functions, damage-repair mechanisms, and associations with various pulmonary and systemic diseases. This review comprehensively summarizes current research progress regarding the biological characteristics of ciliated cells, their functional roles in pulmonary pathophysiology, and therapeutic implications in respiratory disorders. Furthermore, we propose future research directions aiming to provide novel insights for disease prevention/treatment strategies and promote the translation of basic research findings into clinical applications.

Key words: ciliated cells, pulmonary diseases, therapeutics, pharmacological interventions

CLC Number:

R563
R329.2

Lele ZHANG, Guodong ZANG, Wei ZHANG. Research progress on ciliated cells and pulmonary diseases: from basic science to clinical applications[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(7): 1001-1008.

Figures/Tables 1

References 56

1	Ruiz Garcia S, Deprez M, Lebrigand K, et al. Novel dynamics of human mucociliary differentiation revealed by single-cell RNA sequencing of nasal epithelial cultures[J]. Development, 2019, 146 (20): dev177428. doi: 10.1242/dev.177428
2	Bustamante-Marin XM, Ostrowski LE. Cilia and mucociliary clearance[J]. Cold Spring Harb Perspect Biol, 2017, 9 (4): a028064. doi: 10.1016/b0-12-370879-6/00079-x
3	Satir P, Christensen ST. Overview of structure and function of mammalian cilia[J]. Annu Rev Physiol, 2007, 69, 377- 400. doi: 10.1146/annurev.physiol.69.040705.141236
4	Shah AS, Ben-Shahar Y, Moninger TO, et al. Motile cilia of human airway epithelia are chemosensory[J]. Science, 2009, 325 (5944): 1131- 1134. doi: 10.1126/science.1173869
5	Shayan MV, Holmes D, Saha SC, et al. Mucociliary clearance: a review of modelling techniques[J]. J Biomech, 2020, 99, 109578. doi: 10.1016/j.jbiomech.2019.109578
6	Brekman A, Walters MS, Tilley AE, et al. FOXJ1 prevents cilia growth inhibition by cigarette smoke in human airway epithelium in vitro[J]. Am J Respir Cell Mol Biol, 2014, 51 (5): 688- 700. doi: 10.1165/rcmb.2013-0363OC
7	Rayamajhi D, Ege M, Ukhanov K, et al. The forkhead transcription factor Foxj1 controls vertebrate olfactory cilia biogenesis and sensory neuron differentiation[J]. PLoS Biol, 2024, 22 (1): e3002468. doi: 10.1371/journal.pbio.3002468
8	Didon L, Zwick RK, Chao IW, et al. RFX3 modulation of FOXJ1 regulation of cilia genes in the human airway epithelium[J]. Respir Res, 2013, 14 (1): 70. doi: 10.1186/1465-9921-14-70
9	Tsao PN, Vasconcelos M, Izvolsky KI, et al. Notch signaling controls the balance of ciliated and secretory cell fates in developing airways[J]. Development, 2009, 136 (13): 2297- 2307. doi: 10.1242/dev.034884
10	Gerovac BJ, Valencia M, Baumlin N, et al. Submersion and hypoxia inhibit ciliated cell differentiation in a notch-dependent manner[J]. Am J Respir Cell Mol Biol, 2014, 51 (4): 516- 525. doi: 10.1165/rcmb.2013-0237OC
11	Zhou Z, Liang S, Zhou Z, et al. Avasimibe alleviates disruption of the airway epithelial barrier by suppressing the Wnt/β-Catenin signaling pathway[J]. Front Pharmacol, 2022, 13, 795934. doi: 10.3389/fphar.2022.795934
12	Mercey O, Popa A, Cavard A, et al. Characterizing isomiR variants within the microRNA-34/449 family[J]. FEBS Lett, 2017, 591 (5): 693- 705. doi: 10.1002/1873-3468.12595
13	Satarić MV, Nemeš T, Satarić B, et al. Calcium ions tune the beats of cilia and flagella[J]. Biosystems, 2020, 196, 104172. doi: 10.1016/j.biosystems.2020.104172
14	Satarić MV, Zdravković S, Nemeš T, et al. Calcium signaling modulates the dynamics of cilia and flagella[J]. Eur Biophys J, 2020, 49 (7): 619- 631. doi: 10.1007/s00249-020-01471-8
15	Bernstein ZJ, Shenoy A, Chen A, et al. Engineering the IL-4/IL-13 axis for targeted immune modulation[J]. Immunol Rev, 2023, 320 (1): 29- 57. doi: 10.1111/imr.13230
16	Cho HY, Park S, Miller L, et al. Role for mucin-5AC in upper and lower airway pathogenesis in mice[J]. Toxicol Pathol, 2021, 49 (5): 1077- 1099. doi: 10.1177/01926233211004433
17	Hill DB, Button B, Rubinstein M, et al. Physiology and pathophysiology of human airway mucus[J]. Physiol Rev, 2022, 102 (4): 1757- 1836. doi: 10.1152/physrev.00004.2021
18	Guo-Parke H, Linden D, Weldon S, et al. Deciphering respiratory-virus-associated interferon signaling in COPD airway epithelium[J]. Medicina, 2022, 58 (1): 121. doi: 10.3390/medicina58010121
19	Raby KL, Michaeloudes C, Tonkin J, et al. Mechanisms of airway epithelial injury and abnormal repair in asthma and COPD[J]. Front Immunol, 2023, 14, 1201658. doi: 10.3389/fimmu.2023.1201658
20	Ancel J, Belgacemi R, Diabasana Z, et al. Impaired ciliary beat frequency and ciliogenesis alteration during airway epithelial cell differentiation in COPD[J]. Diagnostics, 2021, 11 (9): 1694.
21	Petit LMG, Belgacemi R, Ancel J, et al. Airway ciliated cells in adult lung homeostasis and COPD[J]. Eur Respir Rev, 2023, 32 (170): 230075. doi: 10.1183/16000617.0106-2023
22	Laube BL, Afshar-Mohajer N, Koehler K, et al. Acute and chronic in vivo effects of exposure to nicotine and propylene glycol from an e-cigarette on mucociliary clearance in a murine model[J]. Inhal Toxicol, 2017, 29 (5): 197- 205. doi: 10.1080/08958378.2017.1336585
23	Wang XQ, Hao YJ, Yin YJ, et al. Lianhua Qingke preserves mucociliary clearance in rat with acute exacerbation of chronic obstructive pulmonary disease by maintaining ciliated cells proportion and protecting structural integrity and beat function of cilia[J]. Int J Chron Obstruct Pulmon Dis, 2024, 19, 403- 418. doi: 10.2147/COPD.S436323
24	Stoleriu MG, Ansari M, Strunz M, et al. COPD basal cells are primed towards secretory to multiciliated cell imbalance driving increased resilience to environmental stressors[J]. Thorax, 2024, 79 (6): 524- 537. doi: 10.1136/thorax-2022-219958
25	Thomas B, Koh MS, O'Callaghan C, et al. Dysfunctional bronchial cilia are a feature of chronic obstructive pulmonary disease (COPD)[J]. COPD, 2021, 18 (6): 657- 663. doi: 10.1080/15412555.2021.1963695
26	Maher TM. Interstitial lung disease: a review[J]. JAMA, 2024, 331 (19): 1655- 1665. doi: 10.1001/jama.2024.3669
27	Wijsenbeek M, Suzuki A, Maher TM. Interstitial lung diseases[J]. Lancet, 2022, 400 (10354): 769- 786. doi: 10.1016/S0140-6736(22)01052-2
28	Lipinski JH, Moore BB, O'Dwyer DN. The evolving role of the lung microbiome in pulmonary fibrosis[J]. Am J Physiol Lung Cell Mol Physiol, 2020, 319 (4): L675- L682. doi: 10.1152/ajplung.00258.2020
29	Evans CM, Fingerlin TE, Schwarz MI, et al. Idiopathic pulmonary fibrosis: a genetic disease that involves mucociliary dysfunction of the peripheral airways[J]. Physiol Rev, 2016, 96 (4): 1567- 1591. doi: 10.1152/physrev.00004.2016
30	Otoupalova E, Smith S, Cheng G, et al. Oxidative stress in pulmonary fibrosis[J]. Compr Physiol, 2020, 10 (2): 509- 547. doi: 10.1002/j.2040-4603.2020.tb00120.x
31	Hakeem A, Yang S. Regulation of INPP5E in ciliogenesis, development, and disease[J]. Int J Biol Sci, 2025, 21 (2): 579- 594. doi: 10.7150/ijbs.99010
32	Ni H, Chen M, Dong D, et al. CYLD/HDAC6 signaling regulates the interplay between epithelial-mesenchymal transition and ciliary homeostasis during pulmonary fibrosis[J]. Cell Death Dis, 2024, 15 (8): 581. doi: 10.1038/s41419-024-06972-4
33	Cloutier MM, Dixon AE, Krishnan JA, et al. Managing asthma in adolescents and adults: 2020 asthma guideline update from the National Asthma Education and Prevention Program[J]. JAMA, 2020, 324 (22): 2301- 2317. doi: 10.1001/jama.2020.21974
34	Gay ACA, Banchero M, Carpaij OB, et al. Airway epithelial cell response to RSV is mostly impaired in goblet and multiciliated cells in asthma[J]. Thorax, 2024, 79 (9): 811- 821. doi: 10.1136/thorax-2023-220230
35	Oppova D, Bánovčin P, Ďurdík P, et al. Bronchial asthma and mucociliary clearance—a bidirectional relationship[J]. Curr Respir Med Rev, 2024, 20 (4): 203- 301. doi: 10.2174/011573398x296504240308070338
36	Boomer J, Choi J, Alsup A, et al. Increased Muc5AC and decreased ciliated cells in severe asthma partially restored by inhibition of IL-4Rα receptor[J]. Am J Respir Crit Care Med, 2024, 210 (12): 1409- 1420. doi: 10.1164/rccm.202307-1266OC
37	Ren Y, Su X, Kong L, et al. Therapeutic effects of histone deacetylase inhibitors in a murine asthma model[J]. Inflamm Res, 2016, 65 (12): 995- 1008. doi: 10.1007/s00011-016-0984-4
38	Jesenak M, Durdik P, Oppova D, et al. Dysfunctional mucociliary clearance in asthma and airway remodeling—new insights into an old topic[J]. Respir Med, 2023, 218, 107372. doi: 10.1016/j.rmed.2023.107372
39	Choi H, McShane PJ, Aliberti S, et al. Bronchiectasis management in adults: state of the art and future directions[J]. Eur Respir J, 2024, 63 (6): 2301846.
40	Chen ZG, Li YY, Wang ZN, et al. Aberrant epithelial remodeling with impairment of cilia architecture in non-cystic fibrosis bronchiectasis[J]. J Thorac Dis, 2018, 10 (3): 1753- 1764. doi: 10.21037/jtd.2018.02.13
41	Martinez-Garcia MA, Sierra-Párraga JM, Quintana E, et al. CFTR dysfunction and targeted therapies: a vision from non-cystic fibrosis bronchiectasis and COPD[J]. J Cyst Fibros, 2022, 21 (5): 741- 744. doi: 10.1016/j.jcf.2022.04.018
42	Staar BO, Hegermann J, Auber B, et al. Ciliary ultrastructure assessed by transmission electron microscopy in adults with bronchiectasis and suspected primary ciliary dyskinesia but inconclusive genotype[J]. Cells, 2023, 12 (22): 2628.
43	Fernández-Barat L, Alcaraz-Serrano V, Amaro R, et al. Pseudomonas aeruginosa in bronchiectasis[J]. Semin Respir Crit Care Med, 2021, 42 (5): 587- 594. doi: 10.1007/978-3-319-61452-6_12
44	Perea L, Faner R, Chalmers JD. Pathophysiology and genomics of bronchiectasis[J]. Eur Respir Rev, 2024, 33 (173): 230185.
45	Saito D, Suzuki C, Tanaka S, et al. Ambroxol-enhanced ciliary beating via voltage-gated Ca²⁺ channels in mouse airway ciliated cells[J]. Eur J Pharmacol, 2023, 941, 175496. doi: 10.1016/j.ejphar.2023.175496
46	Li M, Bao JL, Yang L. The clinical efficacy of combining ambroxol hydrochloride with antibiotics for the treatment of chronic bronchitis[J]. Altern Ther Health Med, 2024, 31 (1): 161- 167.
47	Mata M, Sarrion I, Armengot M, et al. Respiratory syncytial virus inhibits ciliogenesis in differentiated normal human bronchial epithelial cells: effectiveness of N-acetylcysteine[J]. PLoS One, 2012, 7 (10): e48037. doi: 10.1371/journal.pone.0048037
48	Frohock JI, Wijkstrom-Frei C, Salathe M. Effects of albuterol enantiomers on ciliary beat frequency in ovine tracheal epithelial cells[J]. J Appl Physiol, 2002, 92 (6): 2396- 2402. doi: 10.1152/japplphysiol.00755.2001
49	Escher A, Kieninger E, De Groof S, et al. In vitro effect of combined hypertonic saline and salbutamol on ciliary beating frequency and mucociliary transport in human nasal epithelial cells of healthy volunteers and patients with cystic fibrosis[J]. J Aerosol Med Pulm Drug Deliv, 2023, 36 (4): 171- 180. doi: 10.1089/jamp.2022.0026
50	Varenyiova Z, Rojas-Hernandez LS, Spano J, et al. Azithromycin promotes proliferation, and inhibits inflammation in nasal epithelial cells in primary ciliary dyskinesia[J]. Sci Rep, 2023, 13 (1): 14453. doi: 10.1038/s41598-023-41577-5
51	张婷, 孙嵘, 杨涌, 等. 慢性阻塞性肺疾病的黏液高分泌机制及治疗[J]. 中国临床药理学与治疗学, 2024, 29 (4): 383- 391. doi: 10.12092/j.issn.1009-2501.2024.04.004
52	Guan YH, Zhang X, Yang HM, et al. Long-term azithromycin treatment in pediatric primary ciliary dyskinesia: a retrospective study[J]. Front Pediatr, 2022, 10, 905253. doi: 10.3389/fped.2022.905253
53	杨静, 席克虎, 桂岩. 18β-甘草酸单铵盐对过敏性鼻炎大鼠鼻黏膜上皮纤毛的影响[J]. 临床耳鼻咽喉头颈外科杂志, 2016, 29 (23): 2060- 2064.
54	张建伟, 窦昌贵, 张勉, 等. 紫菀、款冬及其配伍的毒性及药效学研究[J]. 中国临床药理学与治疗学, 2007, 12 (4): 405- 411. doi: 10.3969/j.issn.1009-2501.2007.04.010
55	班建平, 张川林, 卢峰. 严桂珍教授治疗原发性纤毛不动综合征经验[J]. 福建中医药, 2021, 52 (6): 50- 51. doi: 10.13260/j.cnki.jfjtcm.012271
56	阚书慧, 李朋成, 孔连委, 等. 通调任督针刺法联合孟鲁司特钠治疗咳嗽变异性哮喘[J]. 长春中医药大学学报, 2024, 40 (10): 1111- 1115.

[1]	LI Yadong, YU Qingsong, HE Chao, WANG Jing. Beyond sleep-wake regulation: roles of orexin in cognition and emotion regulation [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2025, 30(11): 1453-1466.
[2]	ZHAO Tingting, LI Junfeng, ZHANG Liting. Progress in the potential therapeutic mechanism of mesenchymal stem cell-derived exosomes for liver fibrosis [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2024, 29(4): 475-480.
[3]	SHAO Hua, HE Zijian, HU Linlin, ZHAN Ying, HU Rongrong, HE Jie. Determination of caspofungin in human plasma by UPLC-MS/MS [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(10): 1133-1137.
[4]	JIN Jianbo, ZHANG Jianhua . Research progress of alopecia experimental model and its pharmacotherapeutics [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(1): 115-120.
[5]	GU Bing, CHENG Xiang, JIN Jian-bo, YU Ri-yue. Animal models for brain ischemia and its application in experimental therapeutics [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(9): 1074-1080.
[6]	FAN Lan, XIE Hai-tang, ZHOU Hong-hao. Herb-drug interactions in oncology and potential mechanisms [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(2): 134-139.
[7]	SHAN Chang-min, LI Juan, LI Pu. Apoptosis and therapeutic for cells of liver cancers SHAN Chang-min, LI Juan, LI Pu [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(8): 851-856.