MicroRNA-195 is downregulated in the peripheral blood of pregnant women with pregnancy-induced hypertension and inhibits the trophoblast apoptosis through targeting iNOS

Reports indicate that pregnancy induced hypertension (PIH) is known to have long term adverse effects both in the mother and offspring. At present, the pathogenesis of PIH is incompletely understood. Recent studies on microRNA (miRNA) offer the possibility for developing a new class of molecular markers for diagnosis of PIH. However, the function of miRNAs in the development of PIH remains unknown. In the present study, differentially expressed miRNAs in the peripheral blood of healthy pregnant women and women with PIH were screened by PCR array and validated using quantitative real-time polymerase chain reaction. Then, the effects of miRNA-195 on the apoptosis of trophoblast cells were assessed by silencing and over-expressing the miRNA. Our study showed that miR-195 was specifically down-regulated in the peripheral blood of women with PIH. We found that overexpression of miR-195 inhibited the apoptosis of trophoblast cells, whereas apoptosis was enhanced by knockdown of miR195. And the activity of caspase 3/8/9 were inhibited or enhanced in trophoblast cells transfected with miR-195 inhibitor or miR-195 mimic. We also confirmed that inducible nitric oxide synthase (iNOS), which playing important roles in cells apoptosis, as a direct target of miR-195 by using the dual-luciferase assay. Furthermore, we found that expression of iNOS was up-regulated in peripheral blood samples from patients with PIH and inversely correlated with miR-195 expression. Our study demonstrated that the miR-195-inhibited apoptosis of trophoblast cells may contribute to PIH and miR-195 can be considered to be a promising therapeutic target for PIH.