Exploring the role and diversity of mucins in health and disease with special insight into non-communicable diseases

Abstract

Mucins are major glycoprotein components of the mucus that coats the surfaces of cells lining the respiratory, digestive, gastrointestinal and urogenital tracts. They function to protect epithelial cells from infection, dehydration and physical or chemical injury, as well as to aid the passage of materials through a tract i.e., lubrication. They are also implicated in the pathogenesis of benign and malignant diseases of secretory epithelial cells. In Human there are two types of mucins, membrane-bound and secreted that are originated from mucous producing goblet cells localized in the epithelial cell layer or in mucous producing glands and encoded by MUC gene. Mucins belong to a heterogeneous family of high molecular weight proteins composed of a long peptidic chain with a large number of tandem repeats that form the so-called mucin domain. The molecular weight is generally high, ranging between 0.2 and 10 million Dalton and all mucins contain one or more domains which are highly glycosylated. The size and number of repeats vary between mucins and the genetic polymorphism represents number of repeats (VNTR polymorphisms), which means the size of individual mucins can differ substantially between individuals which can be used as markers. In human it is only MUC1 and MUC7 that have mucin domains with less than 40% serine and threonine which in turn could reduce number of PTS domains. Mucins can be considered as powerful two-edged sword, as its normal function protects from unwanted substances and organisms at an arm's length while, malfunction of mucus may be an important factor in human diseases. In this review we have unearthed the current status of different mucin proteins in understanding its role and function in various non-communicable diseases in human with special reference to its organ specific locations. The findings described in this review may be of direct relevance to the major research area in biomedicine with reference to mucin and mucin associated diseases.

Calcium-activated Chloride Channel Regulator 1 (CLCA1) Controls Mucus Expansion in Colon by Proteolytic Activity

“…We have however so far not been able to confirm this in vitro . Further, although CLCA1 is primarily expressed by the intestine it has also been reported to be expressed in stomach, uterus and testis in healthy objects, and in diseased lung, which are all covered by mucus suggesting that the role of CLCA1 is associated with mucus, but is not restricted to colon [ 23 , 41 ].…”

Targeting the gut barrier for the treatment of alcoholic liver disease

“…26,27 Mucins can be considered a two-edged sword, as their normal function protects against unwanted substances and microorganism penetration while malfunction of mucins may be a causal factor in disease. 28 In addition to MUC2 secretion, the intestinal goblet cells also secrete a number of other mucus components, including trefoil factor peptide 3 (TFF3), resistin-like molecule β (RELMβ), Fc-γ binding protein (FCGBP), zymogen granule protein 16 (ZG16) and calcium-activated chloride channel regulator 1 (CLCA1), 20,23 all of which contribute to a highly viscous extracellular layer.…”

Infection by Leishmania (Leishmania) infantum chagasi causes intestinal changes B‐1 cells dependent

“…Alterations in cell renewal also affect the goblet cells, 43 since mucins production is dynamic and can be changed due to luminal or intestinal injuries. 44,45 Infections with L (L) infantum chagasi caused changes in the amount of acid goblet cells in XID and XID + B1 animals, thus modifying the intestinal mucus composition. Regarding the XID I group, the number of sulphomucin-producing goblet cells was increased and that of the sialomucins was reduced.…”

“…7,8,12 These events can generate epithelial damage in the intestinal villi, requiring the cellular renewal that leads to less differentiated cells and higher villi. In addition, the quantitative change with regard to the proportion of goblet cells and, consequently to mucus composition, modifies the environment of resident microbiota 45 and intestinal homeostasis.…”