Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350001, Fujian, China.
BMC Pregnancy Childbirth. 2023 Mar 1;23(1):131. doi: 10.1186/s12884-023-05448-1.
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.
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.
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.
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.
子痫前期（PE）是一种妊娠并发症，会给母亲和胎儿带来长期不良后果，甚至可能导致死亡。胎盘氧化应激失衡导致的氧化剂和抗氧化剂，被认为是子痫前期的关键机制之一（与炎症等一起），其中胎盘线粒体起着重要作用。已知缺氧诱导因子-1（HIF-1α）和血管内皮生长因子（VEGF）在子痫前期患者中的表达增加。已知线粒体铁蛋白（FtMt）可保护线粒体免受氧化应激，但其在子痫前期中的具体作用尚不清楚。
我们使用 qRT-PCR 和 Western blot 检测了子痫前期患者胎盘组织中 FtMt、HIF-1α 和 VEGF 的表达水平。还用人绒毛膜滋养细胞进行缺氧处理，然后通过 CCK8、Transwell 和内皮细胞血管生成试验检测细胞增殖、侵袭和血管生成能力；我们还检测了这些细胞中 HIF-1α 和 VEGF 的表达。最后，构建并转染了过表达或抑制 FtMt 慢病毒载体以及阴性对照载体到缺氧处理的人绒毛膜滋养细胞中；然后分析细胞功能。
PE 组 FtMt、HIF-1α 和 VEGF 的表达水平高于对照组（P<0.05）。缺氧后滋养细胞中 HIF-1α 和 VEGF 蛋白表达增加。侵袭能力和血管形成能力增加，细胞增殖能力降低。这些作用被转染 FtMt 敲除慢病毒载体的细胞所逆转。差异有统计学意义。
分析表明，FtMt 在缺氧后子痫前期滋养细胞的血管调节中起关键作用，可能通过 HIF-1α/VEGF 信号通路发挥作用。这些结果使我们对 PE 的发病机制有了更深入的了解，并表明 HIF-1α/VEGF 信号通路是治疗 PE 的新靶点。
