PP13

Galectins are glycan-binding proteins that regulate innate and adaptive immune responses, and some confer maternal-fetal immune tolerance in eutherian mammals. A chromosome 19 cluster of galectins has emerged in anthropoid primates, species with deep placentation and long gestation. Three of the five human cluster galectins are solely expressed in the placenta, where they may confer additional immunoregulatory functions to enable deep placentation. One of these is galectin-13, also known as Placental Protein 13 (PP13). It has a "jelly-roll" fold, carbohydrate-recognition domain and sugar-binding preference resembling other mammalian galectins. PP13 is predominantly expressed by the syncytiotrophoblast and released from the placenta into the maternal circulation. Its ability to induce apoptosis of activated T cells in vitro, and to divert and kill T cells as well as macrophages in the maternal decidua in situ, suggests important immune functions. Indeed, mutations in the promoter and an exon of LGALS13 presumably leading to altered or non-functional protein expression are associated with a higher frequency of preeclampsia and other obstetrical syndromes, which involve immune dysregulation. Moreover, decreased placental expression of PP13 and its low concentrations in first trimester maternal sera are associated with elevated risk of preeclampsia. Indeed, PP13 turned to be a good early biomarker to assess maternal risk for the subsequent development of pregnancy complications caused by impaired placentation. Due to the ischemic placental stress in preterm preeclampsia, there is increased trophoblastic shedding of PP13 immunopositive microvesicles starting in the second trimester, which leads to high maternal blood PP13 concentrations. Our meta-analysis suggests that this phenomenon may enable the potential use of PP13 in directing patient management near to or at the time of delivery. Recent findings on the beneficial effects of PP13 on decreasing blood pressure due to vasodilatation in pregnant animals suggest its therapeutic potential in preeclampsia.

Galectins regulate cell growth, proliferation, differentiation, apoptosis, signal transduction, mRNA splicing, and interactions with the extracellular matrix. Here we focus on the galectins in the reproductive system, particularly on a group of six galectins that first appears in anthropoid primates in conjunction with the evolution of highly invasive placentation and long gestation. Of these six, placental protein 13 (PP13, galectin 13) interacts with glycoproteins and glycolipids to enable successful pregnancy. PP13 is related to the development of a major obstetric syndrome, preeclampsia, a life-threatening complication of pregnancy which affects ten million pregnant women globally. Preeclampsia is characterized by hypertension, proteinuria, and organ failure, and is often accompanied by fetal loss and major newborn disabilities. PP13 facilitates the expansion of uterine arteries and veins during pregnancy in an endothelial cell-dependent manner, via the eNOS and prostaglandin signaling pathways. PP13 acts through its carbohydrate recognition domain that binds to sugar residues of extracellular and connective tissue molecules, thus inducing structural stabilization of vessel expansion. Further, decidual PP13 aggregates may serve as a decoy that induces white blood cell apoptosis, contributing to the mother's immune tolerance to pregnancy. Lower first trimester PP13 level is one of the biomarkers to predict the subsequent risk to develop preeclampsia, while its molecular mutations/polymorphisms that are associated with reduced PP13 expression are accompanied by higher rates of preeclampsia We propose a targeted PP13 replenishing therapy to fight preeclampsia in carriers of these mutations.

Objective: The aim: To investigate role of CD23, VEGF and PP13 in diagnostics of early and late preeclampsia, and their benefit for prediction of preeclampsia. Patients and methods: Materials and methods: Investigation included 40 placentas from deliveries in women with preeclampsia (main group) and 40 placentas from physiological delivery in somatically healthy women, who had no complications during pregnancy (control group). Placentas in the main group were devided into two sub-groups (20 in each) - with early and late preeclampsia. Each group underwent both hystomorphometrical and immunohystochemical investigation with biomarkers CD23, VEGF and PP13. Results: Results: Positive immunohystochemical reaction to PP13 was determined in all samples of syncitiotrophoblast of villi of chorion. Investigations showed that expression of PP13 in sub-groups with early and late preeclampsia was a lot lower comparing to control group (normal pregnancies). Positive immunohystochemical reaction to VEGF was determined in all samples of endothelia of the capillaries of the villi of chorion. Our investigation showed that expression of VEGF in sub-groups with early and late PE was a lot lower comparing to a control group. Immunohystochemical reaction to CD23 was comperatively lower in all samples in endothelia of the capillariesof the villi of chorion and cyncithiotrophoblast. Conclusion: Conclusions: Determined specialties of the expression of angiogenic factors ( PlGF, VEGF, endoglin) and production of PP13, by altered expression of VEGF, PlGF in first trimester of pregnancy, which is associated with lowest production of PP13, accompanied by placental dysfunction and preeclampsia.