Gal-2 Increases H3K4me3 and H3K9ac in Trophoblasts and Preeclampsia

Laura Hahn; Sarah Meister; Mareike Mannewitz; Susanne Beyer; Stefanie Corradini; Uwe Hasbargen; Sven Mahner; Udo Jeschke; Thomas Kolben; Alexander Burges

doi:10.3390/biom12050707

Gal-2 Increases H3K4me³ and H3K9ac in Trophoblasts and Preeclampsia

Biomolecules. 2022 May 15;12(5):707. doi: 10.3390/biom12050707.

Authors

Affiliations

¹ Department of Obsterics and Gynecology, University Hospital, Ludwig-Maximilians-Universität Munich, Marchioninistr. 15, 81337 Munich, Germany.
² Department of Radiation Oncology, University Hospital, Ludwig-Maximilians-Universität Munich, Marchioninistr. 15, 81337 Munich, Germany.
³ Department of Gynecology and Obsterics, University Hospital Augsburg, 86156 Augsburg, Germany.

Abstract

Preeclampsia (PE) is a severe pregnancy disorder with a pathophysiology not yet completely understood and without curative therapy. The histone modifications H3K4me³ and H3K9ac, as well as galectin-2 (Gal-2), are known to be decreased in PE. To gain a better understanding of the development of PE, the influence of Gal-2 on histone modification in trophoblasts and in syncytialisation was investigated. Immunohistochemical stains of 13 PE and 13 control placentas were correlated, followed by cell culture experiments. An analysis of H3K4me³ and H3K9ac was conducted, as well as cell fusion staining with E-cadherin and β-catenin-both after incubation with Gal-2. The expression of H3K4me³ and H3K9ac correlated significantly with the expression of Gal-2. Furthermore, we detected an increase in H3K4me³ and H3K9ac after the addition of Gal-2 to BeWo/HVT cells. Moreover, there was increased fusion of HVT cells after incubation with Gal-2. Gal-2 is associated with the histone modifications H3K4me³ and H3K9ac in trophoblasts. Furthermore, syncytialisation increased after incubation with Gal-2. Therefore, we postulate that Gal-2 stimulates syncytialisation, possibly mediated by H3K4me³ and H3K9ac. Since Gal-2, as well as H3K4me³ and H3K9ac, are decreased in PE, the induction of Gal-2 might be a promising therapeutic target.

Keywords: H3K4me3; H3K9ac; galectin-2; histone modification; preeclampsia; syncytialisation; trophoblasts.

MeSH terms

Cell Fusion
Female
Galectin 2* / metabolism
Histones* / metabolism
Humans
Placenta / metabolism
Pre-Eclampsia* / metabolism
Pregnancy
Trophoblasts* / metabolism

Substances

Galectin 2
Histones

Grants and funding

S.M. (Sarah Meister) is supported by the DFG-funded Clinician Scientist Program PRIME, grant number 413,635,475. S.M. (Sven Mahner): research support, advisory board, honoraria and travel expenses from AbbVie, AstraZeneca, Clovis, Eisai, GlaxoSmithKline, Medac, MSD, Novartis, Olympus, PharmaMar, Roche, Sensor Kinesis, Teva, Tesaro; T.K.: holds stocks in Roche, relative employed at Roche; A.B.: research support, advisory board, honoraria from AstraZeneca, Roche, Tesaro.