Down-Regulation of CPEB4 Alleviates Preeclampsia through the Inhibition of Ferroptosis by PFKFB3.

IF 1.5 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Critical Reviews in Eukaryotic Gene Expression Pub Date : 2024-01-01 DOI:10.1615/CritRevEukaryotGeneExpr.2023048702
Jiao Song, Hailan Yang
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Abstract

Gestational diabetes mellitus (GDM) complicated with preeclampsia can lead to polyhydramnios, ketosis. Herein, we explored that CPEB4 in cancer progression of preeclampsia and its underlying mechanism. All the serum samples were collected from patients with preeclampsia. These was the induction of CPEB4 in patients with preeclampsia. The serum of CPEB4 mRNA expression was positive correlation with Proteinuria, systolic blood pressure and diastolic blood pressure in patients. The serum of CPEB4 mRNA expression was also negative correlation with body weight of infant in patients. The serum of CPEB4 mRNA expression also was negative correlation with GPX4 level and GSH activity level in patients. The serum of CPEB4 mRNA expression was positive correlation with iron content in patients. CPEB4 gene inhibited trophoblast cell proliferation. CPEB4 gene promoted trophoblast cell ferroptosis by mitochondrial damage. CPEB4 gene induced PFKFB3 expression by the inhibition of PFKFB3 Ubiquitination. PFKFB3 inhibitor reduced the effects of CPEB4 on cell proliferation and ferroptosis of trophoblast cell. Taken together, the CPEB4 promoted trophoblast cell ferroptosis through mitochondrial damage by the induction of PFKFB3 expression, CPEB4 as an represents a potential therapeutic strategy for the treatment of preeclampsia or various types of GDM.

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下调 CPEB4 可通过 PFKFB3 抑制铁蜕变缓解子痫前期症状
妊娠期糖尿病(GDM)并发子痫前期可导致多胎妊娠、酮症酸中毒。在此,我们探讨了 CPEB4 在子痫前期癌症进展中的作用及其内在机制。所有血清样本均来自子痫前期患者。这些都是子痫前期患者 CPEB4 的诱导因素。血清中 CPEB4 mRNA 的表达与患者的蛋白尿、收缩压和舒张压呈正相关。患者血清中 CPEB4 mRNA 的表达与婴儿体重呈负相关。患者血清中 CPEB4 mRNA 的表达与 GPX4 水平和 GSH 活性水平也呈负相关。患者血清中 CPEB4 mRNA 的表达与铁含量呈正相关。CPEB4 基因抑制滋养层细胞增殖。CPEB4 基因通过线粒体损伤促进滋养层细胞铁变态反应。CPEB4 基因通过抑制 PFKFB3 泛素化诱导 PFKFB3 的表达。PFKFB3 抑制剂降低了 CPEB4 对滋养层细胞增殖和铁凋亡的影响。综上所述,CPEB4通过诱导PFKFB3的表达,通过线粒体损伤促进滋养层细胞铁析出,CPEB4是治疗子痫前期或各种类型GDM的一种潜在治疗策略。
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来源期刊
Critical Reviews in Eukaryotic Gene Expression
Critical Reviews in Eukaryotic Gene Expression 生物-生物工程与应用微生物
CiteScore
2.70
自引率
0.00%
发文量
67
审稿时长
1 months
期刊介绍: Critical ReviewsTM in Eukaryotic Gene Expression presents timely concepts and experimental approaches that are contributing to rapid advances in our mechanistic understanding of gene regulation, organization, and structure within the contexts of biological control and the diagnosis/treatment of disease. The journal provides in-depth critical reviews, on well-defined topics of immediate interest, written by recognized specialists in the field. Extensive literature citations provide a comprehensive information resource. Reviews are developed from an historical perspective and suggest directions that can be anticipated. Strengths as well as limitations of methodologies and experimental strategies are considered.
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