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核结合蛋白 2/内脂素-1 通过 EGFR-PLCG1-CAMK4 通路影响胎盘发育中的滋养层细胞融合。

Nuclear Binding Protein 2/Nesfatin-1 Affects Trophoblast Cell Fusion during Placental Development via the EGFR-PLCG1-CAMK4 Pathway.

机构信息

Department of Nutrition and Food Hygiene, School of Public Health, Capital Medical University, Beijing 100069, China.

Departments of Health and Nutrition Sciences, Brooklyn College of City University of New York, New York, NY 11210, USA.

出版信息

Int J Mol Sci. 2024 Feb 5;25(3):1925. doi: 10.3390/ijms25031925.

Abstract

Previous studies have shown that nuclear binding protein 2 () is expressed in the human placenta and increases with an increase in the syncytialization of trophoblast cells. This study aimed to investigate the role of in the differentiation and fusion of trophectoderm cells. In this study, the expression levels of and E-cadherin in the placentas of rats at different gestation stages were investigated. The results showed that there was an opposite trend between the expression of placental and E-cadherin in placentas in different trimesters. When primary human trophoblast (PHT) and BeWo cells were treated with high concentrations of Nesfatin-1, the trophoblast cell syncytialization was significantly inhibited. The effects of knockdown in BeWo cells and Forskolin-induced syncytialization were investigated. These cells showed a significantly decreased cell fusion rate. The mechanism underlying -regulated trophoblast cell syncytialization was explored using RNA-Seq and the results indicated that the epidermal growth factor receptor ()-phospholipase C gamma 1 ()-calmodulin-dependent protein kinase IV () pathway might be involved. The results suggested that the placental expression of plays an important role in the fusion of trophoblasts during differentiation via the pathway.

摘要

先前的研究表明,核结合蛋白 2()在人胎盘组织中表达,并随滋养层细胞的合胞体化增加而增加。本研究旨在探讨在滋养层细胞的分化和融合过程中,发挥的作用。在这项研究中,研究了不同妊娠阶段大鼠胎盘组织中表达水平。结果表明,在不同妊娠月份的胎盘组织中,胎盘的表达与 E-钙黏蛋白呈相反趋势。当原代人滋养层(PHT)和 BeWo 细胞用高浓度的 nesfatin-1 处理时,滋养层细胞的合胞体化明显受到抑制。研究了 BeWo 细胞中 knockdown 和 Forskolin 诱导的合胞体化的作用。这些细胞的细胞融合率明显下降。使用 RNA-Seq 探讨了调节滋养层细胞合胞体化的机制,结果表明,表皮生长因子受体()-磷脂酶 C 伽马 1()-钙调蛋白依赖性蛋白激酶 IV()途径可能参与其中。结果表明,胎盘组织中的表达在通过途径的分化过程中对滋养层细胞的融合起着重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da80/10856506/ca08ee1287c8/ijms-25-01925-g001.jpg

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