Placental protein 13 (PP13/galectin-13) undergoes lipid raft-associated subcellular redistribution in the syncytiotrophoblast in preterm preeclampsia and HELLP syndrome

Abstract

Objective To investigate placental protein 13 (PP13) localization in relation to cytoskeleton and lipid rafts in preeclampsia and HELLP syndrome. Study Design Placental cryosections from patients with preeclampsia and HELLP, and controls were stained for PP13, actin, PLAP (lipid raft marker), and CD71 (nonraft marker). BeWo cells exposed to stress conditions were stained for PP13 and actin. Protein localization were investigated by confocal microscopy, PP13 concentrations by ELISA. Results PP13-actin colocalization was increased in syncytiotrophoblast juxtamembrane regions in term/preterm preeclampsia and HELLP. PP13-CD71 colocalization was decreased and PP13-PLAP proximity was increased in preterm but not term preeclampsia and HELLP. PP13-release from BeWo cells was inhibited by cytoskeleton disruption, and augmented by Ca2+-influx and ischemic stress. Conclusion The actin cytoskeleton, probably in connection with lipid rafts, controls trophoblastic “nonclassical” PP13 export. PP13 is released from the syncytiotrophoblast in preterm preeclampsia and HELLP, mimicked in BeWo cells by ischemic stress, suggesting PP13 is a placental alarmin.

Effects of Placental Protein 13 on the Cardiovascular System in Gravid and Non-Gravid Rodents

“…After mid-gestation, serum PP13 levels sharply rise in women who enter the active phase of the pathology due to shedding of syncytiotrophoblast microparticles from damaged placental villi [13,14,19,22,32]. …”

“…Hence, it has been shown that PP13 may act as a marker to predict preeclampsia already in the first trimester of pregnancy. PP13 is secreted from the syncytiotrophoblast after week 5 of gestation, either as single molecule or via shedding of syncytial microparticles [12,13,19]. Therefore, PP13 has been proposed as a specific biomarker and a promising tool to predict preeclampsia in early pregnancy [13,14,15,16,17,18].…”

“…It is released into the intervillous space [13], where it enters the maternal blood stream and can be determined by immunodiagnostic testing of maternal serum [8,11,13,14,15,16,17,18]. In a healthy pregnant woman, serum PP13 concentrations rise moderately from the first to the third trimester of pregnancy.…”

First trimester maternal serum placental protein 13 levels in singleton vs. twin pregnancies with and without severe pre-eclampsia

“…The protein, also known as galectin 13, is exclusively produced in the syncytiotrophoblast layer of the placenta, from where it reaches the maternal blood circulation from as early as the 6 th week of gestation [3,17]. In singleton pregnancies, lower first trimester levels of PP13 can be used, together with other markers, for predicting an individual woman's risk of developing preeclampsia (PE) [14,17,18,26].…”

Placental Protein 13 Administration to Pregnant Rats Lowers Blood Pressure and Augments Fetal Growth and Venous Remodeling

“…In healthy pregnancy, serum PP13 concentrations rise moderately from the first to the third trimester [20]. However, lower first-trimester levels of maternal serum PP13 [12,25,26] and its encoding mRNA [27,28] have been shown not only in cases developing early-onset preeclampsia, but also in those patients developing a severe form of late-onset preeclampsia [13,20]. PP13 has therefore been proposed as a specific biomarker for predicting preeclampsia in early pregnancy [13,23,25,26].…”