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.
Highlights
Galectins are a class of carbohydrate binding proteins with high affinity to β-galactoside sugars that bind to them via their N- or- O-linked glycosylation [1,2]
We know of 20 members of the galectin family that interact with a plethora of molecules involved in inflammation, immune responses, cell trafficking, apoptosis, autophagy, trans-membrane signaling, and interactions with cytosolic and nuclear targets, nuclear transcription, gene expression, or mRNA splicing [18,19,20,21]
It is worth mentioning that the Galectin 10 (Gal 10) protein is expressed by white blood cells (WBC), while its mRNA is exclusively expressed in bone marrow tissues
Summary
Galectins are a class of carbohydrate binding proteins with high affinity to β-galactoside sugars that bind to them via their N- or- O-linked glycosylation [1,2]. They share primary structural homology in their carbohydrate-recognition domains (CRDs) included in a canonical sequence of ~130 amino acid backbone. They are synthesized as cytosolic proteins and reside in the cytosol or nucleus for much of their lifetime [3]. Galectins are incorporated in the development of new therapeutics [22,27,28,29], and some are already in clinical development stages (https://galecto.com/ [30])
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
