Galectin 13 (PP13) Facilitates Remodeling and Structural Stabilization of Maternal Vessels during Pregnancy

Abstract

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.

Transcriptomic analysis of primate placentas and novel rhesus trophoblast cell lines informs investigations of human placentation

“…However, the majority of the DEGs identified here have not been previously reported, thus our results provide novel insight into the molecular differences underlying human and rhesus placentation. For instance, we observed the upregulation of LGALS13 in human compared to rhesus, which encodes a galectin that interacts with glycoproteins and glycolipids to facilitate the expansion of uterine arteries and veins during pregnancy in an endothelial cell-dependent manner via the eNOS and prostaglandin signaling pathways (Sammar et al 2019). Its downregulation in pregnancy disorders is thought to contribute to aberrant uteroplacental blood flow (Sammar et al 2019), while the decreased expression in rhesus placenta may underlie differences in the extent and depth of human versus rhesus placental invasion or perhaps represent an alternative mechanism for uterine vessel expansion in rhesus.…”

“…For instance, we observed the upregulation of LGALS13 in human compared to rhesus, which encodes a galectin that interacts with glycoproteins and glycolipids to facilitate the expansion of uterine arteries and veins during pregnancy in an endothelial cell-dependent manner via the eNOS and prostaglandin signaling pathways (Sammar et al 2019). Its downregulation in pregnancy disorders is thought to contribute to aberrant uteroplacental blood flow (Sammar et al 2019), while the decreased expression in rhesus placenta may underlie differences in the extent and depth of human versus rhesus placental invasion or perhaps represent an alternative mechanism for uterine vessel expansion in rhesus. Our results also suggest that recently-evolved highly-expressed human placental genes may contribute to an increased risk of aberrant EVT invasion associated with pre-eclampsia (Brosens et al 2011); however, further evolutionary and functional investigation of these genes are required to determine this.…”

Cerebrospinal Fluid of Preeclamptic and Normotensive Pregnant Women Compared to Nonpregnant Women Analyzed with Mass Spectrometry

“…For instance, Calcyclin (S100A6) and Galectin 13 (PP13) are both calcium-binding proteins that have been mentioned before to be involved in PE. 28 , 29 Calcium and magnesium are administered to PE women. The literature shows that the administration of calcium might have some beneficial effect, but is not a remedy.…”

Potential Protein Biomarkers for Preeclampsia

“…PP13 has a high affinity for sugar residues, such as the sugar residues of AB and B antigens in the ABO blood group. It can play an essential role in pregnancy by interacting with glycoproteins and glycolipids, including promoting uterine arteriovenous dilatation during pregnancy and maintaining the stability of maternal vascular structure [32]. Some studies have found that the serum PP13 in patients with PE is low during early pregnancy, which can be considered as a biomarker to predict PE [33][34][35].…”