A potential role for tissue kallikrein-related peptidases in human cervico-vaginal physiology

2008 ◽  
Vol 389 (6) ◽  
Author(s):  
Julie L.V. Shaw ◽  
Eleftherios P. Diamandis
Keyword(s):  
Epithelial Cells ◽  
Serine Proteases ◽  
Physiological Role ◽  
Matrix Proteins ◽  
Fetal Membrane ◽  
Vaginal Fluid ◽  
Tissue Kallikrein ◽  
Vaginal Epithelial Cells ◽  
Skin Physiology

AbstractHuman 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.

Pathophysiology of genetic deficiency in tissue kallikrein activity in mouse and man

2013 ◽  
Vol 110 (09) ◽  
pp. 476-483 ◽  
Author(s):  
Ludovic Waecke ◽  
Louis Potier ◽  
Christine Richer ◽  
Ronan Roussel ◽  
Nadine Bouby ◽  
...  
Keyword(s):  
Human Subjects ◽  
Physiological Role ◽  
Tissue Kallikrein ◽  
Site Mutation ◽  
Cardiac Ischaemia ◽  
Kinin Receptors ◽  
At1 Receptor Antagonists ◽  
Kallikrein Activity ◽  
Deficient Mice

SummaryStudy of mice rendered deficient in tissue kallikrein (TK) by gene inactivation and human subjects partially deficient in TK activity as consequence of an active site mutation has allowed recognising the physiological role of TK and its peptide products kinins in arterial function and in vasodilatation, in both species. TK appears as the major kinin forming enzyme in arteries, heart and kidney. Non-kinin mediated actions of TK may occur in epithelial cells in the renal tubule. In basal condition, TK deficiency induces mild defective phenotypes in the cardiovascular system and the kidney. However, in pathological situations where TK synthesis is typically increased and kinins are produced, TK deficiency has major, deleterious consequences. This has been well documented experimentally for cardiac ischaemia, diabetes renal disease, peripheral ischaemia and aldosterone-salt induced hypertension. These conditions are all aggravated by TK deficiency. The beneficial effect of ACE/kininase II inhibitors or angiotensin II AT1 receptor antagonists in cardiac ischaemia is abolished in TK-deficient mice, suggesting a prominent role for TK and kinins in the cardioprotective action of these drugs. Based on findings made in TK-deficient mice and additional evidence obtained by pharmacological or genetic inactivation of kinin receptors, development of novel therapeutic approaches relying on kinin receptor agonism may be warranted.

scholarly journals TACSTD2 upregulation is an early reaction to lung infection

2021 ◽  
Author(s):  
Sara Lenart ◽  
Peter Lenart ◽  
Hana Kotasova ◽  
Vendula Pelkova ◽  
Veronika Sedlakova ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Physiological Role ◽  
Lung Epithelial Cells ◽  
Antibody Drug Conjugate ◽  
Epithelial Barrier Function ◽  
Transcriptomic Data ◽  
Transmembrane Glycoprotein ◽  
Lung Epithelial ◽  
Evolutionarily Conserved

TACSTD2 encodes a transmembrane glycoprotein Trop2 commonly overexpressed in carcinomas. While the Trop2 protein was discovered already in 1981 and first antibody-drug conjugate targeting Trop2 were recently approved cancer therapy, the physiological role of Trop2 is still not fully understood. In this article, we show that TACSTD2/Trop2 expression is evolutionarily conserved in lungs of various vertebrates. By analysis of publicly available transcriptomic data we demonstrate that TACSTD2 level consistently increases in lungs infected with miscellaneous pathogens. Single cell and subpopulation based transcriptomic data revealed that the major source of TACSTD2 transcript are lung epithelial cells and their progenitors and that TACSTD2 is induced directly in lung epithelial cells following infection. This increase may represent a mechanism to maintain/restore epithelial barrier function and contribute to regeneration process in infected/damaged lungs.

scholarly journals Glycodelin mRNA is expressed in the genital tract of male and female rats (Rattus norvegicus)

1999 ◽  
Vol 23 (1) ◽  
pp. 57-66 ◽  
Author(s):  
C Keil ◽  
B Husen ◽  
J Giebel ◽  
G Rune ◽  
R Walther
Keyword(s):  
Epithelial Cells ◽  
Reproductive Tract ◽  
In Situ Hybridisation ◽  
Physiological Role ◽  
Reproductive Organs ◽  
Female Rats ◽  
Male And Female Rats ◽  
First Time

In the present study we demonstrate for the first time the expression of glycodelin mRNA in the female and male genital tracts of rats using non-radioactive in situ hybridisation. Glycodelin fragment 1 (+41 to +141) shares 100% homology with the human gene sequence. In the ovary, glycodelin mRNA was restricted to granulosa cells. In the uterus, glycodelin mRNA was expressed in all epithelial cells of the endometrium. In the male reproductive tract, glycodelin mRNA was distributed in all epithelial cells of the epididymis, the prostate and the seminal vesicle. However, in the testis, glycodelin mRNA was predominantly found in spermatogonia and in spermatocytes of the seminiferous epithelium. The expression in several reproductive organs of rats offers an excellent tool to study further the physiological role of glycodelin, which is so far thought to act as an immunosuppressive factor.

Mannose-binding lectin is produced by vaginal epithelial cells and its level in the vaginal fluid is influenced by progesterone

2010 ◽  
Vol 48 (1-3) ◽  
pp. 281-286 ◽  
Author(s):  
R. Bulla ◽  
F. De Seta ◽  
O. Radillo ◽  
C. Agostinis ◽  
P. Durigutto ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mannose Binding Lectin ◽  
Vaginal Fluid ◽  
Vaginal Epithelial Cells ◽  
Mannose Binding ◽  
Binding Lectin

scholarly journals Adhesion of Tritrichomonas foetus to Bovine Vaginal Epithelial Cells

1999 ◽  
Vol 67 (8) ◽  
pp. 3847-3854 ◽  
Author(s):  
B. N. Singh ◽  
J. J. Lucas ◽  
D. H. Beach ◽  
S. T. Shin ◽  
R. O. Gilbert
Keyword(s):  
Epithelial Cells ◽  
Cell Surface ◽  
Trichomonas Vaginalis ◽  
Host Cells ◽  
Tritrichomonas Foetus ◽  
Trypan Blue Exclusion ◽  
Vaginal Epithelial Cells ◽  
Host Parasite

ABSTRACT An in vitro culture system of bovine vaginal epithelial cells (BVECs) was developed to study the cytopathogenic effects ofTritrichomonas foetus and the role of lipophosphoglycan (LPG)-like cell surface glycoconjugates in adhesion of parasites to host cells. Exposure of BVEC monolayers to T. foetusresulted in extensive damage of monolayers. Host cell disruption was measured quantitatively by a trypan blue exclusion assay and by release of 3H from [3H]thymidine-labeled host cells. Results indicated contact-dependent cytotoxicity of host cells byT. foetus. The cytopathogenic effect was a function ofT. foetus density. Metronidazole- or periodate-treatedT. foetus showed no damage to BVEC monolayers. A related human trichomonad, Trichomonas vaginalis, showed no cytotoxic effects, indicating species-specific host-parasite interactions. A direct binding assay was developed and used to investigate the role of a major cell surface LPG-like molecule in host-parasite adhesion. The results of competition experiments showed that the binding to BVECs was displaceable, was saturable, and yielded a typical binding curve, suggesting that specific receptor-ligand interactions mediate the attachment of T. foetus to BVECs. Progesterone-treated BVECs showed enhanced parasite binding. T. foetus LPG inhibited the binding of T. foetus to BVECs; the LPG from T. vaginalis and a variety of other glycoconjugates did not. These data imply specificity of LPG on host-parasite adhesion. Periodate-treated parasites showed no adherence to host cells, indicating the involvement of carbohydrate containing molecules in the adhesion process.

scholarly journals Genetic deficiency in tissue kallikrein activity in mouse and man: effect on arteries, heart and kidney

2008 ◽  
Vol 389 (6) ◽  
Author(s):  
Anne Pizard ◽  
Christine Richer ◽  
Nadine Bouby ◽  
Nicolas Picard ◽  
Pierre Meneton ◽  
...  
Keyword(s):  
Renal Tubule ◽  
Human Subjects ◽  
Critical Role ◽  
Physiological Role ◽  
Tissue Kallikrein ◽  
Protective Effects ◽  
Mouse Mutants ◽  
Kallikrein Activity ◽  
Deficient Mice

AbstractTissue kallikrein (KLK1) is a kinin-forming serine protease synthesized in many organs including arteries and kidney. Study of the physiological role of KLK1 has benefited from the availability of mouse and human genetic models of KLK1 deficiency, through engineering ofKLK1mouse mutants and discovery of a major polymorphism in the humanKLK1gene that induces a loss of enzyme activity. Studies in KLK1-deficient mice and human subjects partially deficient in KLK1 have documented its critical role in arterial function in both species. KLK1 is also involved in the control of ionic transport in the renal tubule, an action that may not be kinin-mediated. Studies of experimental diseases in KLK1-deficient mice have revealed cardio- and nephro-protective effects of KLK1 and kinins in acute cardiac ischemia, post-ischemic heart failure, and diabetes. Potential clinical and therapeutic developments are discussed.

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

2008 ◽  
Vol 389 (12) ◽  
Author(s):  
Julie L.V. Shaw ◽  
Constantina Petraki ◽  
Carole Watson ◽  
Alan Bocking ◽  
Eleftherios P. Diamandis
Keyword(s):  
Host Defense ◽  
Reproductive System ◽  
Serine Proteases ◽  
Cervical Mucus ◽  
Vaginal Fluid ◽  
Tissue Kallikrein ◽  
Hormonal Changes ◽  
Female Reproductive System ◽  
Antimicrobial Proteins

AbstractHuman 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 vitrocleavage 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 vitrocleavage 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.

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