FtMt reduces oxidative stress-induced trophoblast cell dysfunction via the HIF-1α/VEGF signaling pathway

Abstract

Background Preeclampsia (PE) is a complication of pregnancy that causes long-term adverse outcomes for the mother and fetus and may even lead to death. Oxidative stress caused by the imbalance of oxidants and antioxidants in the placenta has been considered as one of the key mechanisms of preeclampsia (together with inflammation, etc.), in which the placental mitochondria play an important role. The expression of hypoxia-inducible factor-1 (HIF-1α) and vascular endothelial growth factor (VEGF) is known to be increased in patients with PE. Mitochondrial ferritin (FtMt) is known to protect the mitochondria from oxidative stress, although its specific role in PE remains unclear. Methods We used qRT-PCR and western blotting to detect the expression levels of FtMt, HIF-1α, and VEGF in placental tissues from patients with PE. Human chorionic trophoblast cells were also administered with hypoxia treatment, followed by the detection of cell proliferation, invasion and angiogenic capacity by CCK8, Transwell, and endothelial cell angiogenesis assays; we also detected the expression of HIF-1α and VEGF in these cells. Finally, overexpression or inhibitory FtMt lentiviral vectors, along with negative control vectors, were constructed and transfected into hypoxia-treated human chorionic trophoblast cells; this was followed by analyses of cell function. Results The expression levels of FtMt, HIF-1α and VEGF in the PE group were higher than those in the control group (P < 0.05). Following hypoxia, there was an increase in the expression levels of HIF-1α and VEGF protein in trophoblast cells. There was also an increase in invasion ability and vascular formation ability along with a reduction in cell proliferation ability. These effects were reversed by transfecting cells with the knockout FtMt lentivirus vector. The differences were statistically significant. Conclusion Analyses showed that FtMt plays a key role in the vascular regulation of PE trophoblast cells after hypoxia possibly acting via the HIF-1α/VEGF signaling pathway. These results provide us an enhanced understanding of the pathogenesis of PE and suggest that the HIF-1α/VEGF signaling pathway represents a new target for the treatment of PE.

HSPB8 binding to c-Myc alleviates hypoxia/reoxygenation-induced trophoblast cell dysfunction

“…It has been reported that mitochondria are the main sites of ROS production and mitochondrial membrane integrity is sensitive to the cellular ROS levels ( 41 ). In the present study, H/R stimulation led to suppressed proliferation, migration, invasion and elevated ROS and JC-1 monomer levels of HTR-8/SVneo cells, suggesting the damage caused by trophoblast cell dysfunction and induction of oxidative stress, which were consistent with the results of previous studies ( 17 , 42 , 43 ). At present, HSPB8 has been confirmed to be highly expressed in various human tumors and HSPB8 overexpression has been demonstrated to facilitate the proliferation, migration and invasion of these cancer cells, such as prostate cancer, gastric cancer and lung adenocarcinoma ( 44-46 ).…”

The mechanism of Shoutai Wan in the treatment of recurrent spontaneous abortion - A review

“…Additionally, the hypoxic environment within the placenta creates optimal conditions for trophoblast invasion and placenta formation, while changes in oxygen partial pressure adversely affect the proliferation and invasive capacity of trophoblasts [ 24 ]. A study [ 25 ] has shown significant changes in the expression levels of Vascular Endothelial Growth Factor (VEGF) and Hypoxia-Inducible Transcription Factor 1- α (HIF-1 α ) in the chorionic tissues of patients with early RSA. STW, by decreasing the expression level of HIF-1 α mRNA and protein and simultaneously promoting the expression of VEGF and its receptor mRNA and protein, enhances the proliferation and reinforces functions of placental trophoblast cells.…”

Phenylbutyric acid inhibits hypoxia‐induced trophoblast apoptosis and autophagy in preeclampsia via the PERK/ATF‐4/CHOP pathway

“…It showed that the protective effect of 4-PBA on hypoxia-induced trophoblast cells was linked to autophagy inhibition and PERK/ATF-4/CHOP pathway downregulation. Some studies have suggested that placental hypoxia is a significant pathological change in PE(Xu et al, 2023). The placental trophoblast cells, which are the main cells in the placenta, function in invasion and vascular recast and maintain the normal development of the placenta(Zhang et al, 2020).…”