Upregulation of P53 promoted G1 arrest and apoptosis in human umbilical cord vein endothelial cells from preeclampsia

Abstract

Objective Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality. Current research has focused on endothelial dysfunction regarding pathogenesis of preeclampsia. However, very limited or no studies so far have been performed to assess possible damaged endothelial cell growth/development in the placenta–umbilical cord circulation system in human preeclampsia. Methods We isolated and cultured human umbilical cord vein endothelial cells (HUVECs) from normal and preeclampsia pregnancies in vitro. We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay to measure cell growth and flow cytometric analysis to determine cell-cycle distribution. Annexin V-fluorescein isothiocyanate/propidium iodide double staining was employed for cell apoptosis experiments. Results The study showed that the cell growth was significantly suppressed, accompanied by the increased G1 arrest and apoptosis in cultured HUVECs from preeclampsia pregnancies comparing with normotensive controls. Protein P53 was upregulated in the cultured HUVECs from preeclampsia pregnancies, which induced G1 arrest, followed by upregulating P21 expression, and downregulating cyclin E expression and CDK2–cyclin E complexes. On the other hand, upregulation of P53 also activated Bax gene and repressed Bcl-2 and BIRC5 genes, resulting in an increase of the Bax/Bcl-2 ratio and subsequently activating caspase cascade, ultimately led to an initiation of the apoptotic machinery. Conclusion These results indicated that in preeclampsia, vascular endothelial cells could be damaged and cellular proliferation was depressed in human placenta–umbilical cord circulation, adding new information on endothelial cell injury for better understanding the pathogenesis of preeclampsia.

Long Non-coding RNA Gas5 Is Associated With Preeclampsia and Regulates Biological Behaviors of Trophoblast via MicroRNA-21

“…Further, HTR-8/SVneo cell line was selected which was closer to the villous cells in first-trimester placenta. According to the prediction of KEGG (Kyoto Encyclopedia of Genes and Genomes) bioinformatics database, we detected the alteration of the PI3K/AKT signaling pathway downstream proteins MMP9 and TP53, which were closely related with preeclampsia (Gao et al, 2016;Chen and Khalil, 2017), after GAS5 expression changed. The results showed that the expressions of MMP9 and TP53 were all regulated up and down statistically according to the activation of PI3K/AKT signaling pathway by qRT-PCR ( Figure 6C).…”

Is there a role for placental senescence in the genesis of obstetric complications and fetal growth restriction?

“…In preeclamptic placentas, the formation of telomere (or nuclear) aggregate (SAHF) is increased compared with placentas from normotensive women 24,28,106 The expression of senescence inducers p53, p21, and p16 are higher in pregnancy complicated by preeclampsia. 27,[107][108][109] Moreover, a high level of proinflammatory cytokine (IL-1b and IL-6) profile can be demonstrated in preeclampsia. 27,110 DNA oxidation as measured by the expression of 8-OHdG in preeclamptic placenta is higher than in the healthy placentas.…”

In vivo inhibitory effect of suberoylanilide hydroxamic acid combined with sorafenib on human hepatocellular carcinoma cells

“…p53 gene has the function of monitoring cell genome integrity, blocking cell proliferation and promoting cell apoptosis. When the cell cycle DNA is damaged at a certain time, p53 starts the related repair mechanism, and if the repair fails, the cell death program is initiated to remove the mutant cells (Gao et al, 2016). In the present study, the expression level of Bcl-2 protein in SAHA+sorafenib group was significantly lower than that in other groups (P < 0.05), and the expression levels of Bax and p53 protein in SAHA+sorafenib group were significantly higher than those in other groups, respectively (P < 0.05).…”