炎症诱导pfkfb3介导的糖酵解通过PI3K-Akt-mTOR途径促进早产小鼠肌层收缩。

IF 5 2区 生物学 Q2 CELL BIOLOGY
Jing He, Xuan Li, Huihui Yu, Chenyi Xu, Ruixian Tian, Ping Zhou, Zongzhi Yin
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引用次数: 0

摘要

炎症是早产的重要危险因素。炎症增强了各种细胞类型的糖酵解过程,并有助于肌收缩的发展。然而,炎症激活妊娠小鼠子宫平滑肌细胞(mUSMCs)糖酵解的潜力及其在促进炎症性早产中的作用仍未被探索。本研究采用脂多糖建立细胞和动物炎症模型。我们发现妊娠晚期mUSMCs的炎症可以启动糖酵解并促进细胞收缩。随后,使用糖酵解抑制剂2-脱氧葡萄糖抑制糖酵解可以逆转炎症诱导的细胞收缩。脂多糖刺激后,6-磷酸果糖激酶2激酶(PFKFB3)在mUSMCs中的表达显著上调。此外,还观察到乳酸积累和增强的收缩。抑制PFKFB3逆转了由炎症引起的乳酸积累和增强收缩。我们还发现炎症激活了磷脂酰肌醇3-激酶(PI3K) -蛋白激酶B (Akt) -哺乳动物雷帕霉素靶蛋白(mTOR)通路,导致PFKFB3表达上调。PI3K-Akt通路抑制剂LY294002和mTOR通路抑制剂Rapamycin可有效抑制PFKFB3蛋白表达上调、乳酸生成以及脂多糖诱导的细胞收缩增强。本研究表明,炎症通过PI3K-Akt-mTOR通路调控PFKFB3,从而增强妊娠mUSMCs的糖酵解过程,最终导致子宫肌收缩。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Inflammation-induced PFKFB3-mediated glycolysis promoting myometrium contraction through the PI3K-Akt-mTOR pathway in preterm birth mice.

Inflammation is a significant risk factor for preterm birth. Inflammation enhances glycolytic processes in various cell types and contributes to the development of myometrial contractions. However, the potential of inflammation to activate glycolysis in pregnant murine uterine smooth muscle cells (mUSMCs) and its role in promoting inflammatory preterm birth remain unexplored. In this study, lipopolysaccharide was employed to establish both cell and animal inflammation models. We found that inflammation of mUSMCs during late pregnancy could initiate glycolysis and promote cell contraction. Subsequently, the inhibition of glycolysis using the glycolysis inhibitor 2-deoxyglucose can reverse inflammation-induced cell contraction. The expression of 6-phosphofructokinase 2 kinase (PFKFB3) was significantly upregulated in mUSMCs following lipopolysaccharide stimulation. In addition, lactate accumulation and enhanced contraction were observed. Inhibition of PFKFB3 reversed the lactate accumulation and enhanced contraction induced by inflammation. We also found that inflammation activated the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt)-mammalian target of the rapamycin (mTOR) pathway, leading to the upregulation of PFKFB3 expression. The PI3K-Akt pathway inhibitor LY294002 and the mTOR pathway inhibitor rapamycin effectively inhibited the upregulation of PFKFB3 protein expression, lactate production, and the enhancement of cell contraction induced by lipopolysaccharide. This study indicates that inflammation regulates PFKFB3 through the PI3K-Akt-mTOR pathway, which enhances the glycolytic process in pregnant mUSMCs, ultimately leading to myometrial contraction.NEW & NOTEWORTHY Expression of PFKFB3, a key enzyme in glycolysis, was significantly upregulated both in the mUSMCs and myometrium of mice during late pregnancy after lipopolysaccharide stimulation. Activation of the PI3K-Akt-mTOR pathway enhanced PFKFB3 expression, which is involved in the initiation of glycolysis. Inflammation-activated PFKFB3 via the PI3K-Akt-mTOR pathway, which enhances the cellular glycolytic process and thus promotes myometrium contraction in pregnancy.

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来源期刊
CiteScore
9.10
自引率
1.80%
发文量
252
审稿时长
1 months
期刊介绍: The American Journal of Physiology-Cell Physiology is dedicated to innovative approaches to the study of cell and molecular physiology. Contributions that use cellular and molecular approaches to shed light on mechanisms of physiological control at higher levels of organization also appear regularly. Manuscripts dealing with the structure and function of cell membranes, contractile systems, cellular organelles, and membrane channels, transporters, and pumps are encouraged. Studies dealing with integrated regulation of cellular function, including mechanisms of signal transduction, development, gene expression, cell-to-cell interactions, and the cell physiology of pathophysiological states, are also eagerly sought. Interdisciplinary studies that apply the approaches of biochemistry, biophysics, molecular biology, morphology, and immunology to the determination of new principles in cell physiology are especially welcome.
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