title: Influence of gestational diabetes mellitus on human umbilical vein endothelial cell miRNA.
abstract: We aimed to identify miRNAs whose expression levels in fetal tissues are altered by exposure to a diabetic milieu and elucidate the impact on target protein expression. Gestational diabetes mellitus (GDM) affects both immediate and future disease risk in the offspring. We hypothesized that GDM alters miRNA expression in human umbilical vein endothelial cells (HUVECs) that may influence metabolic processes. A cross-sectional design compared differences in miRNA expression in HUVECs and target protein abundance in placentae between infants of women with GDM (IGDM) and infants born to normoglycaemic controls. miRNAs were identified using microarray profiling and literature review and validated by quantitative PCR (qPCR). In vitro transfection studies explored the impact of the miRNA on target protein expression. Expression of seven miRNA species, miR-30c-5p, miR-452-5p, miR-126-3p, miR-130b-3p, miR-148a-3p, miR-let-7a-5p and miR-let-7g-5p, was higher in the HUVECs of IGDM. Abundance of the catalytic subunit of AMP-activated protein kinase α1 (AMPKα1) was decreased in the HUVECs and BeWo cells (transformed trophoblast cell line) transfected with miR-130b and miR-148a mimics. AMPKα1 expression was also decreased in placental tissues of IGDM. The expression of several miRNAs were altered by in utero exposure to DM in infants of women whose dysglycaemia was very well controlled by current standards. Decreased expression of AMPKα1 as a result of increased levels of miR-130b and miR-148a may potentially explain the decrease in fat oxidation we reported in infants at 1 month of age and, if persistent, may predispose offspring to future metabolic disease.
authors: Department of Pediatrics, Section of Diabetes/Endocrinology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, U.S.A.
authors: Jeanie B
authors: JB
authors: Tryggestad
authors: Department of Pediatrics, Division of Endocrinology, University of Illinois College of Medicine, Peoria, IL 61603, U.S.A.
authors: Anu
authors: A
authors: Vishwanath
authors: Department of Pediatrics, Section of Diabetes/Endocrinology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, U.S.A.
authors: Shaoning
authors: S
authors: Jiang
authors: Department of Pediatrics, Section of Diabetes/Endocrinology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, U.S.A.
authors: Ashwini
authors: A
authors: Mallappa
authors: Department of Pediatrics, Section of Diabetes/Endocrinology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, U.S.A.
authors: April M
authors: AM
authors: Teague
authors: Department of Medicine, Section of Endocrinology and Diabetes, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, U.S.A.
authors: Yusuke
authors: Y
authors: Takahashi
authors: Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, U.S.A.
authors: David M
authors: DM
authors: Thompson
authors: Department of Pediatrics, Section of Diabetes/Endocrinology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, U.S.A. steven-chernausek@ouhsc.edu.
authors: Steven D
authors: SD
authors: Chernausek
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D016640:Diabetes, Gestational / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D014327:Trophoblasts / Q000378:metabolism; D055815:Young Adult
chemical_list: D035683:MicroRNAs
keywords: fetal programming; gestational diabetes; human umbilical vein endothelial cell (HUVEC); miRNA