title: Post-transcriptional down regulation of ICAM-1 in feto-placental endothelium in GDM.
abstract: Maternal gestational diabetes (GDM) is associated with hyperglycaemia and hyperinsulinemia in the fetal circulation which consequently may induce endothelial dysfunction in the feto-placental vasculature. In fact, feto-placental vasculature reveals various morphological changes in response to GDM. The cell adhesion molecules (CAMs) ICAM-1, VCAM-1 and E-selectin promote attachment and trans-endothelial migration of leukocytes, and are up regulated in inflammation and endothelial dysfunction. Thus, we hypothesized that the GDM environment upregulates ICAM-1, VCAM-1 and E-selectin in the feto-placental endothelium. We isolated primary feto-placental endothelial cells (fpEC) after normal (n=18) and GDM pregnancy (n=11) and analyzed mRNA (RT-qPCR) and protein expression (Immunoblot) of ICAM-1, VCAM-1 and E-selectin. While other CAMs were unchanged on mRNA and protein levels, ICAM-1 protein was decreased by GDM. Further analysis revealed also a decrease in the release of soluble ICAM-1 (sICAM-1), whose levels correlated negatively with maternal BMI. We conclude that this reduction of ICAM-1 protein species is the result of post-translational regulation, since ICAM-1 mRNA expression was unchanged. In fact, miRNAs targeting ICAM-1 were upregulated in GDM fpEC. Immunohistochemistry showed weaker ICAM-1 staining in the placental endothelium after GDM pregnancies, and demonstrated ICAM-1 binding partners CD11a and CD18 expressed on leukocytes in fetal circulation and on placental tissue macrophages. This study identified reduction of ICAM-1 protein in fpEC in GDM pregnancy, which was regulated post-transcriptionally. Low ICAM-1 protein production may represent a protective, placenta-specific mechanism to avoid leukocyte transmigration into the placenta in response to GDM.
authors.affiliation: a Department of Obstetrics and Gynecology , Medical University of Graz , Austria.
authors.forename: Francisca Isidora
authors.initials: FI
authors.lastname: Díaz-Pérez
authors.affiliation: a Department of Obstetrics and Gynecology , Medical University of Graz , Austria.
authors.forename: Ursula
authors.initials: U
authors.lastname: Hiden
authors.affiliation: b Institute of Cell Biology, Histology and Embryology, Medical University of Graz , Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Gauster
authors.affiliation: b Institute of Cell Biology, Histology and Embryology, Medical University of Graz , Austria.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Lang
authors.affiliation: c Institute of Experimental and Clinical Pharmacology, Medical University of Graz , Austria.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Konya
authors.affiliation: c Institute of Experimental and Clinical Pharmacology, Medical University of Graz , Austria.
authors.forename: Akos
authors.initials: A
authors.lastname: Heinemann
authors.affiliation: a Department of Obstetrics and Gynecology , Medical University of Graz , Austria.
authors.forename: Jelena
authors.initials: J
authors.lastname: Lögl
authors.affiliation: d Cancer and Disease Epigenetics, Murdoch Children's Research Institute , Parkville , Victoria , Australia.|e Department of Pediatrics , University of Melbourne , Victoria , Australia.
authors.forename: Richard
authors.initials: R
authors.lastname: Saffery
authors.affiliation: a Department of Obstetrics and Gynecology , Medical University of Graz , Austria.
authors.forename: Gernot
authors.initials: G
authors.lastname: Desoye
authors.affiliation: a Department of Obstetrics and Gynecology , Medical University of Graz , Austria.
authors.forename: Silvija
authors.initials: S
authors.lastname: Cvitic
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D016640:Diabetes, Gestational / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics*; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005333:Fetus / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism; D044967:Serum / Q000378:metabolism; D012995:Solubility; D014158:Transcription, Genetic
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D035683:MicroRNAs; D021122:Protein Subunits; D018799:Intercellular Adhesion Molecule-1
keywords: E-selectin; GDM; ICAM-1; VCAM-1; endothelial dysfunction; feto-placental endothelium