Abstract P612: TLR3-Induced Placental miR-155 Contributes to Preeclampsia by Augmenting Inflammation
Hypertensive disorders of pregnancy including preeclampsia (PE) affect ~15% of all pregnancies. We have previously demonstrated that excessive maternal immune system activation via Toll-like receptor 3 (TLR3) contributes to the development of PE-like symptoms such as hypertension, endothelial dysfunction, and proteinuria in mice only when pregnant. Recently, increased miR-155 (an inflammation-related miRNA) expression was reported in placentas from women with PE compared to normotensive women suggesting a pathophysiological role of miR-155 in PE. Whether miRNAs play a role in the etiology of PE by augmenting inflammation is unknown. We confirmed miR-155 expression was up-regulated in placentas of poly I:C (a TLR3 agonist) treated wild type mice by microarray (P-PIC: 1.56 fold, p<0.5 vs controls) and qRT-PCR analyses (P-PIC: 3.15 fold, p<0.05 vs. controls). Based on our data we hypothesized that TLR3 activation induces placental miR-155 expression that augments maternal inflammation leading to PE. Transcription factors NF-κB and AP-1 which are known to bind to the promoter of miR-155 were increased in placentas of P-PIC mice. TargetScan, a target identification algorithm predicted suppressor of cytokine signaling 1 (SOCS1) as a putative target of miR-155. SOCS1 prevents overactivation of immune responses but failed to increase in P-PIC mice. ICAM, a marker of inflammation increased significantly in P-PIC mice. P-PIC TLR3 KO mice did not develop hypertension and proteinuria as well as did not exhibit increased placental levels of NF-κB, AP-1, miR-155 expression and ICAM or decreased levels of SOCS1. To determine the placental etiology, human cytotrphoblasts (CTBs) were treated with poly I:C and NF-κB, AP-1 transcription factor levels and miR-155 expression were increased significantly while SOCS1 levels decreased. Together, these data suggest that TLR3 activation increases placental miR-155 expression which downregulates SOCS1 levels and increases inflammation which may contribute to the development of PE.
Author Disclosures: K.R. Bounds: None. C.P. Crutsinger: None. V.L. Chiasson: None. P. Chatterjee: None.
- © 2015 by American Heart Association, Inc.