Mesotrypsinogen

Mesotrypsinogen is the zymogen (inactive precursor) of mesotrypsin, a trypsin-like serine protease produced in the human pancreas. It is encoded by the PRSS3 gene and belongs to the trypsinogen family, which also includes cationic and anionic trypsinogens. In pancreatic acinar cells, mesotrypsinogen is secreted as an inactive proenzyme that is activated by proteolytic cleavage to mesotrypsin, typically initiated by trypsin in the digestive enzyme cascade.

Mesotrypsin is unusual among human trypsins for its relatively broad substrate specificity and its resistance to inhibition by many serine protease inhibitors, such as BPTI and aprotinin. This inhibitor resistance allows mesotrypsin to cleave substrates that are poorly cleaved by other trypsins, including certain protein inhibitors and components of the extracellular matrix, and can influence proteolytic remodeling in physiological and pathological contexts.

Physiologically, mesotrypsinogen and mesotrypsin contribute to digestive processes, but their roles are less dominant than those of cationic and anionic trypsin. In pathological conditions, aberrant expression or activity of mesotrypsin has been linked to cancer progression in some tissues, where it can promote invasion and metastasis by remodeling the extracellular environment and activating other proteases. As a consequence, mesotrypsin and its zymogen are studied as potential therapeutic targets, with research focusing on selective inhibitors to limit mesotrypsin activity.