TLR3-induced placental miR-210 down-regulates the STAT6/interleukin-4 pathway. Academic Article uri icon


  • Several clinical studies have reported increased placental miR-210 expression in women with PE compared to normotensive women, but whether miR-210 plays a role in the etiology of PE is unknown. We reported that activation of TLR3 produces the PE-like symptoms of hypertension, endothelial dysfunction, and proteinuria in mice only when pregnant, but whether TLR3 activation in pregnant mice and human cytotrophoblasts (CTBs) increases miR-210 and modulates its targets related to inflammation are unknown. Placental miR-210 levels were increased significantly in pregnant mice treated with the TLR3 agonist poly I:C (P-PIC). Both HIF-1 and NF-Bp50, known to bind the miR-210 promoter and induce its expression, were also increased significantly in placentas of P-PIC mice. Target identification algorithms and gene ontology predicted STAT6 as an inflammation-related target of miR-210 and STAT6 was decreased significantly in placentas of P-PIC mice. IL-4, which is regulated by STAT6 and increases during normotensive pregnancy, failed to increase in serum of P-PIC mice. P-PIC TLR3 KO mice did not develop hypertension and placental HIF-1, NF-Bp50, miR-210, STAT6, and IL-4 levels were unchanged. To determine the placental etiology, treatment of human CTBs with poly I:C significantly increased HIF-1, NF-Bp50, and miR-210 levels and decreased STAT6 and IL-4 levels. Overexpression of miR-210 in CTBs decreased STAT6 and IL-4 while inhibition of miR-210 increased STAT6 and IL-4. These findings demonstrate that TLR3 activation induces placental miR-210 via HIF-1 and NF-Bp50 leading to decreased STAT6 and IL-4 levels and this may contribute to the development of PE.

published proceedings

  • PLoS One

author list (cited authors)

  • Kopriva, S. E., Chiasson, V. L., Mitchell, B. M., & Chatterjee, P.

citation count

  • 46

complete list of authors

  • Kopriva, Shelley E||Chiasson, Valorie L||Mitchell, Brett M||Chatterjee, Piyali

editor list (cited editors)

  • Thomas, P. G.

publication date

  • July 2013