Journal of Glycobiology
Open Access

O-linked Glycosylation and its Impact on Mucin Function in Respiratory Diseases

Einar Filip^{* *}Correspondence: Einar Filip, Department of Biochemistry, University of Tromso, Tromso, Norway, Email:

Author info »

Description

O-linked glycosylation is an important post-translational modification where carbohydrate chains are attached to the hydroxyl group of serine or threonine residues in proteins. This modification is particularly prevalent in mucins, large glycoproteins found in the mucosal lining of the respiratory, digestive, and other epithelial tissues. Mucins play an essential role in protecting the respiratory tract from pathogens, toxins, and mechanical damage by trapping particles in mucus and facilitating their removal through the mucociliary clearance system. However, changes in the pattern or quantity of O-linked glycosylation can significantly impact mucin function and contribute to the pathophysiology of respiratory diseases. As our understanding of these processes advances, it becomes clear that modifying O-linked glycosylation could offer new route for therapeutic strategies in treating conditions like Chronic Obstructive Pulmonary Disease (COPD), asthma, Cystic Fibrosis (CF), and respiratory infections.

Role of mucins in respiratory health

Mucins are highly glycosylated proteins that form the backbone of mucus, a gel-like substance produced by the epithelial cells lining the respiratory tract. The structure of mucins consists of a protein core decorated with an extensive array of sugar chains, with O-linked glycosylation being a predominant feature. These sugar chains not only contribute to the physical properties of mucus but also play an essential role in mucin's biological function. The hydrophilic nature of O-linked glycans imparts the mucus with its characteristic viscosity and elasticity, essential for trapping pathogens and particles while also enabling clearance through coughing or ciliary action. The proper glycosylation of mucins is vital for maintaining the integrity of the airway surface liquid, a thin layer that facilitates normal mucociliary function. Any disruption in the glycosylation process can lead to changes in mucus composition, viscosity, and clearance, contributing to airway obstruction and the development of respiratory diseases.

Impact of altered O-linked glycosylation in respiratory diseases

In respiratory diseases such as COPD, asthma, and CF, alterations in O-linked glycosylation are often observed. These modifications can affect mucin's properties, resulting in thickened mucus that is difficult to clear from the lungs, a sign of these diseases.

Asthma: In asthma, chronic inflammation leads to an overproduction of mucus by goblet cells in the airways. The increased mucus is often more viscous due to altered O-linked glycosylation, which changes the sugar chain composition on mucins. This modification can lead to mucus hypersecretion, airway obstruction, and difficulty in clearing inhaled allergens or pathogens. Studies have shown that asthma patients exhibit a higher expression of certain enzymes involved in O-linked glycosylation, which could contribute to the abnormal mucin production. Targeting these enzymes might be a potential therapeutic strategy to reduce mucus hypersecretion and improve airway function .

COPD: COPD, a progressive disease marked by airflow limitation and chronic inflammation, is associated with altered mucin glycosylation patterns. In COPD, mucins produced in the lungs often have a higher density of shorter sugar chains, which results in less hydrated mucus. This makes the mucus more sticky and less effective at trapping and removing pathogens, contributing to airway obstruction and bacterial colonization. Furthermore, changes in O-linked glycosylation patterns of mucins in COPD are thought to enhance mucin aggregation, exacerbating airway blockages and increasing the risk of chronic infections .

CF: In CF, a genetic disorder that leads to defective chloride ion transport, the respiratory tract experiences thick, dehydrated mucus that cannot be cleared effectively. O-linked glycosylation plays a significant role in this process. In CF, mucins often exhibit abnormal glycosylation, including changes in the length and branching of the glycan chains. This results in mucus that is both hyper viscous and prone to dehydration, further compromising mucociliary clearance. The altered glycosylation of mucins in CF may also influence the interactions of the mucus with inflammatory cells, exacerbating the chronic inflammation that characterizes the disease.

Conclusion

In conclusion, O-linked glycosylation is a key player in the function and regulation of mucins, which are integral to the health of the respiratory system. Alterations in the glycosylation of mucins contribute to the pathogenesis of several chronic respiratory diseases, including asthma, COPD, and cystic fibrosis. These changes often result in mucus hypersecretion,ncreased viscosity, and impaired mucociliary clearance, leading to airway obstruction and chronic inflammation. As our understanding of O-linked glycosylation and its impact on mucin function deepens, the potential for developing targeted therapies to modulate this process grows. Whether through enzyme inhibitors, gene therapies, or mucolytic agents, targeting O-linked glycosylation could provide a novel approach to managing and treating respiratory diseases. As research continues to explore these possibilities, the future holds potential for more effective and customized treatments that address the root causes of mucus dysfunction, improving the quality of life for individuals with chronic respiratory conditions