The silencing of ApoC3 suppresses oxidative stress and inflammatory responses in placenta cells from mice with preeclampsia via inhibition of the NF-κB signaling pathway.

Graphical abstract The molecular mechanism involving silenced APOC3 regulating the oxidative stress and inflammatory responses in placenta cells of preeclampsia mice via inhibition of the NF-κB signaling pathway. In preeclampsia mice, up-regulated APOC3 increased the expression of p65 and inhibited the expression of phosphorylation of IkBα, thus resulting in the oxidative stress injury and inflammatory responses of placenta cells. While silenced APOC3 could decrease the expression of hs-CPR, IL-6 and TNF-α and the level of MDA, 8-isoprostane and ox-LDL but increase the activity of MMP-2 and MMP-9, so that promoted the survival but inhibited the apoptosis of placenta cells, and then the oxidative stress injury was reduced and cell inflammation was reduced. Highlights • The inhibitory effect of APOC3 silencing on NF-κB signaling pathway is studied. • APOC3 silencing alleviates the progression of mice in preeclampsia. • NF-κB signaling pathway regulates the oxidative stress and inflammatory responses. • APOC3 silencing suppresses NF-κB signaling pathway. • This study provides therapeutic target for preeclampsia. Abstract Objective Preeclampsia is one of the three primary causes of maternal morbidity and mortality worldwide. This study evaluated ApoC3 in placenta cells of mice with preeclampsia to explore its therapeutic role in preeclampsia and assess its function on oxidative stress and inflammatory responses involving the NF-κB signaling pathway. Methods A mouse model of preeclampsia was successfully established. APOC3-siRNA with the best silencing effect was screened out. The expression levels of ApoC3, p65, and IkBα were evaluated. The effect of ApoC3 silencing on metabolic activity and apoptosis was measured. The level of high-sensitivity C-reactive protein (hs-CPR), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α), the activity of matrix metalloproteinase (MMP)-2 and MMP-9, and the expression of malondialdehyde (MDA), 8-isoprostane and oxidized low-density lipoprotein (ox-LDL) were determined. Results ApoC3-siRNA-3 was the most effective siRNA. The mRNA expression of ApoC3 was scarcely observed, while the expression of p65 decreased and the expression of p-IkBα increased in the ApoC3-siRNA group. Compared with those in the model and empty vector groups, the cell apoptosis rate and the activities of invasion-related factors MMP-2 and MMP-9 increased, while the levels of hs-CPR, IL-6, TNF-α, MDA, 8-isoprostane, and ox-LDL decreased in the ApoC3-siRNA group. Conclusion Silencing ApoC3 could suppress the NF-κB signaling pathway, thereby exercising a protective effect on cell injury induced by oxidative stress and reducing inflammatory responses. [ABSTRACT FROM AUTHOR]