We confirmed that both PRSS3 and V1 contain caseinolytic and gelatinolytic activity at 25 kDa. PRSS3 represents,10% of total trypsinogen in normal pancreatic juice. PRSS3 is resistant to SBTI, PSTI, and BPTI sensitive to PMSF and TLCK, and requires proteolytic activation by enterokinase. A new alternative form of PRSS3 was reported in differentiated cultured keratinocytes and was named trypsinogen 5. Unlike the relatively broader distribution of another alternative isoform, trypsinogen 5 was restricted to the brain, small intestine, uterus and keratinocytes. Both trypsinogen 4 and 5 differ only in the Nterminus and both produce active PRSS3 upon cleavage by enteropeptidase, which is shown to be expressed in the granular layer of the epidermis. Therefore, V1 may undergo proteolytic activation by other enzymes in vaginal epithelial cells. The process of enteropeptidase activation is important in regulation of PRSS protease activity both in the pancreas and in cancer cells in which addition of enteropeptidase enhanced cellmediated proteolysis. Currently, the molecular mechanisms of V1 activation are not known. In addition to enteropeptidase, MMP-9 is also known to activate trypsinogen family members in the pancreas. Proteases play a crucial role in extracellular matrix remodeling through their proteolytic action on collagens, proteoglycans, fibronectin, elastin and laminin. The vaginal epithelium represents a major purchase 66547-09-9 interface between the external environment and the female reproductive tract. It is constantly exposed to proteolytic enzymes from many sources, including UNC1999 bacteria in the vaginal vault and immune cells in the lamina propria and subepithelium. Controlled proteolytic activity is thereby important for maintainance of normal tissue turnover and maintenance of this barrier. It is plausible that the V1 proteolytic activity may contribute to the pathophysiology of POP. A similar trypsinogen secreted from cancer cell lines, degrades subendothelial cell extracellular matrix and it has been shown that enzymes similar to PRSS3 degrade fibronectin and aggrecan. Recently, another serine protease termed HTRA1 with a highly conserved trypsin-like protease domain similar to PRSS3 was shown to alter Bruch��s Membrane composition in vivo
