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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

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Role of tissue kallikrein-related peptidases in cervical mucus remodeling and host defense

Julie L.V. Shaw1 / Constantina Petraki2 / Carole Watson3 / Alan Bocking4 / Eleftherios P. Diamandis5

1Department of Pathology and Laboratory Medicine and Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto M5T 3L9, ON, Canada and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto M5G 1L5, ON, Canada

2Department of Pathology, Evangelismos Hospital, GR-10676 Athens, Greece

3Department of Obstetrics and Gynecology, University of Toronto and Mount Sinai Hospital, Toronto M5G 1L5, ON, Canada

4Department of Obstetrics and Gynecology, University of Toronto and Mount Sinai Hospital, Toronto M5G 1L5, ON, Canada

5Department of Pathology and Laboratory Medicine and Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto M5T 3L9, ON, Canada, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto M5G 1L5, ON, Canada and Department of Clinical Biochemistry, University Health Network/Toronto Medical Laboratories, Toronto M5G 2C4, ON, Canada

Corresponding author

Citation Information: Biological Chemistry. Volume 389, Issue 12, Pages 1513–1522, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: 10.1515/BC.2008.171, October 2008

Publication History:
Received:
2008-07-16
Accepted:
2008-09-08
Published Online:
2008-10-09

Abstract

Human tissue kallikrein-related peptidases (KLKs) are 15 hormonally regulated genes on chromosome 19q13.4 encoding secreted serine proteases. Many KLKs are expressed throughout the female reproductive system and found in cervico-vaginal fluid (CVF). Immunohistochemistry was performed to determine KLK localization in the female reproductive system (fallopian tube, endometrium, cervix and vagina tissues). KLK levels were measured in CVF and saliva over the menstrual cycle to study whether KLKs are regulated by hormonal changes during the cycle. In vitro cleavage analysis was performed to establish whether KLKs may play a role in vaginal epithelial desquamation, mucus remodeling or processing of antimicrobial proteins. KLKs were localized in the glandular epithelium of the fallopian tubes and endometrium, the cervical mucus-secreting epithelium and vaginal stratified squamous epithelium. KLK levels peaked in CVF and saliva after ovulation. In vitro cleavage analysis confirmed KLKs 5 and 12 as capable of digesting desmoglein and desmocollin adhesion proteins and cervical mucin proteins 4 and 5B. KLK5 can digest defensin-1α, suggesting it may aid in cervico-vaginal host defense. We provide evidence of potential physiological roles for KLKs in cervico-vaginal physiology: in desquamation of vaginal epithelial cells, remodeling of cervical mucus and processing of antimicrobial proteins.

Keywords: cervical mucus; cervico-vaginal fluid; desquamation; fertility; kallikrein; mucin

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