| First Author | Kopriva SE | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 7 | Pages | e67760 |
| PubMed ID | 23844087 | Mgi Jnum | J:204308 |
| Mgi Id | MGI:5532235 | Doi | 10.1371/journal.pone.0067760 |
| Citation | Kopriva SE, et al. (2013) TLR3-induced placental miR-210 down-regulates the STAT6/interleukin-4 pathway. PLoS One 8(7):e67760 |
| abstractText | 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-1alpha and NF-kappaBp50, 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-1alpha, NF-kappaBp50, 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-1alpha, NF-kappaBp50, 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-1alpha and NF-kappaBp50 leading to decreased STAT6 and IL-4 levels and this may contribute to the development of PE. |
