The association between MUC5AC and MUC5B genes expression and remodeling progression in severe neutrophilic asthma: A direct relationship

• Published in: Respiratory medicine Vol. 213; p. 107260
• Main Authors: Khorasani, Amirhossein Mohajeri, Mohammadi, Bita, Saghafi, Mohammad Reza, Mohammadi, Samane, Ghaffari, Shadi, Mirsadraee, Majid, Khakzad, Mohammad Reza
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-07-2023
• Subjects: Airway remodeling; Airway wall thickness; Asthma - complications; Humans; Lung - metabolism; MUC5AC; MUC5B; Mucin 5AC - genetics; Mucin 5AC - metabolism; Mucin-5B - genetics; Mucin-5B - metabolism; Mucociliary Clearance - physiology; Respiratory Physiological Phenomena; Severe neutrophilic asthma; Sputum - metabolism; Airway remodeling; Severe neutrophilic asthma; MUC5B; MUC5AC; Airway wall thickness
• ISSN: 0954-6111; 1532-3064
• DOI: 10.1016/j.rmed.2023.107260

MUC5 dysregulation is a hallmark of severe neutrophilic asthmatic patients. This study investigates the expression of MUC5AC and MUC5B at mRNA levels on asthma severity and airway wall thickness in severe neutrophilic asthmatic patients.
In this case-control clinical trial, twenty-five severe neutrophilic asthmatic patients and ten control subjects were enrolled. Subjects underwent ACT, pulmonary functions tests, and fractional exhaled nitric oxide (FENO). Also, induced sputum has been obtained to assess the expression of MUC5AC and MUC5B by the real-time PCR. In addition, the thickness of the airway wall was assessed by high-resolution computed tomography (HRCT), and bioinformatic analysis was implemented to approve the selection of the appropriate genes and for further investigations.
A significant difference was observed between the asthmatic and control in MUC5AC and MUC5B mRNA expression. Meanwhile, the expression of MUC5AC increased remarkably by asthma severity; also, it is associated with airway wall thickness (WT) (both P-value <0.05). The expression of MUC5B in asthmatic patients was lower than in control. There is no significant correlation between MUC5B mRNA level and WT and asthma severity. Notably, MUC5AC transcription level was correlated to sputum neutrophil percentage, while MUC5B transcription level had a positive correlation with sputum macrophages and a negative one with sputum neutrophils.
In severe neutrophilic asthma, airway wall thickness increases with MUC5AC mRNA overexpression, which is probably related to asthma severity and the formation of mucus plugs. However, the expression of MUC5B was decreased, resulting in poor mucociliary clearance in the airways.
IR.IAU.MSHD.REC.1400.124
•Dysregulation of MUC5AC and MUC5B expression could be one of the most critical factors in severe asthma progression.•MUC5AC mRNA is upregulated in severe neutrophilic asthmatic patients and could result in the formation of mucus plugs. While MUC5B is downregulated at the transcription level, it demonstrates poor mucociliary clearance in the airways.•Airway wall thickness has been associated with higher levels of MUC5AC mRNA, so the development of MUC5AC mucosal plugs can aggravate airflow obstruction.