MUC5AC

Fig1. Regulation of MUC5AC production. (Ashish Manne, 2023)

What is MUC5AC protein?

MUC5AC gene (mucin 5AC, oligomeric mucus/gel-forming) is a protein coding gene which situated on the short arm of chromosome 11 at locus 11p15. MUC5AC is a high molecular weight mucin, MUC5AC is mainly expressed in the goblet cells of the airway and forms a gel-like mucus in the airway secretions. This mucus is essential for protecting the airways from pathogens and particles, as it is able to trap these foreign substances and clear them through the wiggling of the cilia. The MUC5AC protein is consisted of 5654 amino acids and MUC5AC molecular weight is approximately 585.6 kDa.

What is the function of MUC5AC protein?

The MUC5AC protein is a mucin produced in the respiratory tract, and its main function is to form a protective mucus layer on the surface of the airway to help trap and remove inhaled particles, pathogens, and other foreign substances. Proper regulation of this mucus is essential for maintaining respiratory health, but in certain disease states, such as asthma and chronic obstructive pulmonary disease, overexpression of MUC5AC can lead to abnormal buildup of mucus in the airway, which affects respiratory function and leads to airway obstruction.

MUC5AC related signaling pathway

The expression and regulation of MUC5AC protein are involved in a variety of signaling pathways, including the role of nuclear factor κB (NF-κB), the epidermal growth factor receptor (EGFR) signaling pathway, and Th2 cytokines such as interleukin-13 (IL-13). These signaling pathways are activated in response to inflammation, infection, and tissue damage, resulting in increased transcription of the MUC5AC gene, which in turn produces more MUC5AC proteins in the airway epithelium, forming mucus. This excess production and secretion of mucus is closely related to the pathological process of respiratory diseases such as asthma and chronic obstructive pulmonary disease, in which the accumulation and increased viscosity of mucus can lead to airway obstruction and dysfunction.

MUC5AC related diseases

MUC5AC is an important mucin in respiratory mucus, and its abnormal expression is associated with a variety of airway mucus hypersecretion diseases, such as asthma, chronic obstructive pulmonary disease (COPD), chronic sinusitis, etc. Abnormal expression of MUC5AC is not only involved in the inflammatory response of these diseases, but also may lead to difficulties in the clearance of airway mucus and the formation of mucus plugs, thus affecting respiratory function. Studies have shown that MUC5AC is closely associated with lung lesions and may be a potential target for the treatment of these diseases. For example, by inhibiting the expression of MUC5AC or promoting its clearance, it may help improve airway obstruction and lung function. In addition, the expression of MUC5AC is regulated by many factors, including infection, inflammatory factors, environmental pollutants, etc., which can achieve the regulation of its expression at multiple levels such as transcriptional, post-transcriptional and epigenetic.

Bioapplications of MUC5AC

rhMUC5AC has a variety of potential uses in biomedical research and clinical applications. It can be used to study the physiological and pathological processes of airway mucus, including mucus secretion, viscosity and clearance mechanisms. rhMUC5AC could also be used to develop and test new treatments, particularly for those involving abnormalities in airway mucus, such as chronic obstructive pulmonary disease (COPD), asthma, and other respiratory conditions. By using rhMUC5AC, researchers can better understand disease mechanisms and potentially discover novel therapeutic agents that regulate the expression or function of MUC5AC. These studies contribute to the development of targeted therapeutic strategies for airway inflammation and mucus hypersecretion, thereby improving patient outcomes and quality of life.

Case Study 1: Aindrias Ryan, 2015

Mucins, complex glycoproteins that form mucus, are difficult to manipulate and express in mammalian cells due to their large size and multiple domains, including O-glycosylation sites. Researchers successfully produced recombinant MUC5AC, a key mucin in the respiratory tract, in various forms, including full-length with tandem repeat sequences, in both tracheal and bronchial cell lines. The N-terminus showed potential for branched structures, while the C-terminus underwent cleavage, polymerization, and glycosylation, resembling native MUC5AC processing. Secretion was influenced by the extracellular environment, with the secreted form of the protein showing molecular mass differences, suggesting further processing.

Fig1. Western immunoblots demonstrating expression of recombinant MUC5AC protein.

Fig2. Oligomerization of recombinant MUC5AC N+C and N+2TR+C proteins.

Case Study 2: Xiaojuan Wu, 2024

Chronic obstructive pulmonary disease (COPD) results from exposure to harmful substances like air pollution and cigarette smoke, with excessive mucus production, particularly MUC5AC, being a key feature. This study explored how cigarette smoke extract (CSE) affects MUC5AC expression and the role of reactive oxygen species (ROS) in this process using Calu-3 cells. Researchers measured MUC5AC and MUC5B levels through qRT-PCR, immunofluorescence, and ELISA, and assessed ROS and Ca2+ levels. They also analyzed the expression of IP3R, IRE1α, p-IRE1α, and XBP1s proteins. Silencing IP3R with siRNA reduced CSE-induced effects, and N-acetyl-l-cysteine (NAC) treatment mitigated CSE's impact on ROS, Ca2+, UPR activation, and MUC5AC overexpression.

Fig3. The expression of MUC5AC in Calu-3 cells by immunofluorescence staining.

Fig4. The expression of MUC5AC in culture supernatants was determined by ELISA after transfection with IP3R-siRNA.

MUC5AC has several biochemical functions, for example, extracellular matrix structural constituent. Some of the functions are cooperated with other proteins, some of the functions could acted by MUC5AC itself. We selected most functions MUC5AC had, and list some proteins which have the same functions with MUC5AC. You can find most of the proteins on our site.

MUC5AC has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with MUC5AC here. Most of them are supplied by our site. Hope this information will be useful for your research of MUC5AC.

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