Abstract 668: Deficiency of miR-155 Attenuates TLR3-Induced Preeclampsia-Like Symptoms in Mice Academic Article uri icon


  • Preeclampsia (PE) is one of the leading causes of maternal morbidity and mortality worldwide. PE is diagnosed by new onset hypertension and proteinuria or end-organ damage at or after mid-gestation. Although it is known that excessive maternal inflammation contributes to PE, the underlying mechanisms that cause hypertension during pregnancy are still unclear. Excessive maternal inflammation may be in part mediated by ligation of Toll-like receptors (TLRs) by pathogen- or danger-associated molecular patterns. MicroRNAs are small endogenous regulators of gene expression and recently numerous inflammation-related microRNAs have been identified. Several clinical studies reported that miR-155 expression, which is known to regulate inflammation in various disease conditions, is also up-regulated in the placentas of women with PE. We confirmed by qRT-PCR that miR-155 expression was significantly increased in formalin-fixed paraffin-embedded placentas from patients with PE compared to normal pregnant women. Poly I:C (a TLR3 agonist) treatment of human placental cytotrophoblasts (CTBs) for 24 hours significantly increased miR-155 expression compared to vehicle-treated CTBs. Based on these data we hypothesized that TLR3 activation induces placental miR-155 expression which in turn contributes to excessive maternal inflammation leading to PE whereas miR-155 deficiency will attenuate PE-like symptoms in a TLR3-induced PE mouse model. Pregnant WT and miR-155 KO mice were treated with poly I:C or saline on gestational days (gd) 13, 15, and 17 prior to sacrifice on gd 18. Poly I:C treatment induced hypertension in pregnant WT mice (P-PIC WT) (gd 17 SBP: 1394 mmHg) compared to P WT mice (994 mmHg), however this was attenuated in P-PIC miR-155 KO mice (1001 mmHg ). P-PIC WT mice exhibited endothelial dysfunction and splenomegaly compared to P WT mice and these were also attenuated in PPIC miR-155 KO mice. Our data taken together suggest that miR-155 plays a role in the pathogenesis of PE likely by increasing the maternal inflammatory response.

published proceedings

  • Hypertension

author list (cited authors)

  • Charles, D., Jamison, A., Chiasson, V. L., Mitchell, B. M., & Chatterjee, P.

citation count

  • 0

complete list of authors

  • Charles, Derek||Jamison, Ashley||Chiasson, Valorie L||Mitchell, Brett M||Chatterjee, Piyali

publication date

  • September 2014