Sexual dimorphism of miRNA signatures in feto-placental endothelial cells is associated with altered barrier function and actin organization
| Autor: | Elisa Weiß, Ivana Sreckovic, Andrea Thüringer, Silvija Cvitic, Christian Wadsack, Karl Kashofer, Eva Bernhart, Jasmin Strutz, Waltraud Brandl, Carolin Schliefsteiner, Ursula Hiden, Luciana Lassance, Hannah M Appel |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Placenta 030204 cardiovascular system & hematology Biology Biological pathway Adherens junction 03 medical and health sciences Fetus 0302 clinical medicine Pregnancy microRNA Gene expression medicine Humans Endothelial dysfunction Barrier function Sex Characteristics Endothelial Cells Estrogens General Medicine medicine.disease Actins Cell biology Endothelial stem cell Sexual dimorphism Diabetes Gestational MicroRNAs 030104 developmental biology Female |
| Zdroj: | Clinical Science. 134:39-51 |
| ISSN: | 1470-8736 0143-5221 |
| Popis: | Endothelial function and the risk for endothelial dysfunction differ between males and females. Besides the action of estrogen, sex chromosome gene expression and programming effects also provoke this sexual dimorphism. MicroRNAs (miRNAs) have emerged as regulators of endothelial cell function and dysfunction. We here hypothesized distinct miRNA expression patterns in male versus female human endothelial cells that contribute to the functional differences. We used our well-established model of fetal endothelial cells isolated from placenta (fpEC) and analyzed sexual dimorphic miRNA expression and potentially affected biological functions. Next-generation miRNA sequencing of fpEC isolated after pregnancies with male and female neonates identified sex-dependent miRNA expression patterns. Potential biological pathways regulated by the altered set of miRNAs were determined using mirPath and mirSystem softwares, and suggested differences in barrier function and actin organization. The identified pathways were further investigated by monolayer impedance measurements (ECIS) and analysis of F-actin organization (Phalloidin). Nine miRNAs were differentially expressed in fpEC of male versus female neonates. Functional pathways most significantly regulated by these miRNAs included ‘Adherens junction’, ‘ECM receptor interaction’ and ‘Focal adhesion’. These pathways control monolayer barrier function and may be paralleled by altered cytoskeletal organization. In fact, monolayer impedance was higher in fpEC of male progeny, and F-actin staining revealed more pronounced peripheral stress fibers in male versus female fpEC. Our data highlight that endothelial cell function differs between males and females already in utero, and that altered miRNAs are associated with sex dependent differences in barrier function and actin organization. |
| Databáze: | OpenAIRE |
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