Mechanism of Mucin secretion and the associated pathologies of COPD and cystic fibrosis

Mucins are major components of the mucus layer, which is the first line of the innate defensive system in the respiratory and gastrointestinal tracts. Therefore, alterations in mucin levels can lead to pathological situations like chronic respiratory or intestinal diseases. There are twenty different mucins expressed by human tissues that can be classified into two groups: a) the plasma membrane bound mucins, or b) the gel-forming mucins. Nevertheless, how these heavily glycosylated proteins are released from goblet cells remains largely unclear.

Previously, our group has identified sixteen proteins as putative regulators of MUC5AC secretion in HT29 colonic cells; among them we described the role of the sodium channel TRPM5 in this calcium-regulated process (Mitrovic et al, 2013).

Our current focus is to understand the role of these proteins in MUC5AC secretion by both colonic and bronchial goblet cells. Moreover, we study MUC5AC secretion and its regulation not only in healthy situations, but also under pathological conditions such as cystic fibrosis using cells derived from patients. We are extending our studies to use lung organoids to address the mechanism of mucus homeostasis.

Altogether, our research line will reveal new mechanisms and components of MUC5AC secretion; and, importantly, provide novel pharmacological targets for mucin-related pathologies, such as asthma, cystic fibrosis and Crohn’s disease.