Julie L.V. Shaw, 11Department of Pathology and Laboratory Medicine, and Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 60 Murray Street, Toronto M5T 3L9, ON, Canada and Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Banting Institute, 100 College Street, Toronto M5G 1L5, ON, Canada
Eleftherios P. Diamandis, 22Department of Pathology and Laboratory Medicine, and Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 60 Murray Street, Toronto M5T 3L9, ON, Canada and Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Banting Institute, 100 College Street, Toronto M5G 1L5, ON, Canada
Abstract
Human tissue kallikrein-related peptidases (KLK) are a family of 15 genes located on chromosome 19q13.4 that encode secreted serine proteases with trypsin- and/or chymotrypsin-like activity. Relatively large levels of many KLKs are present in human cervico-vaginal fluid (CVF) and in the supernatant of cultured human vaginal epithelial cells. Many KLKs are also hormonally regulated in vaginal epithelial cells, particularly by glucocorticoids and estrogens. The physiological role of KLK in the vagina is currently unknown; however, analysis of the CVF proteome has revealed clues for potential KLK functions in this environment. Here, we detail potential roles for KLKs in cervico-vaginal physiology. First, we suggest that KLKs play a role in the vagina similar to their role in skin physiology: (1) in the desquamation of vaginal epithelial cells, similar to their activity in the desquamation of skin corneocytes; and (2) in their ability to activate antimicrobial proteins in CVF as they do in sweat. Consequently, we hypothesize that dysregulated KLK expression in the vagina could lead to the development of pathological conditions such as desquamative inflammatory vaginitis. Second, we propose that KLKs may play a role in premature rupture of membranes and pre-term birth through their cleavage of fetal membrane extracellular matrix proteins.
