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小生理电场介导源自 HTR8/SVneo 细胞的绒毛外滋养层细胞的反应:涉及粘着斑激酶信号转导的激活。

A small physiological electric field mediated responses of extravillous trophoblasts derived from HTR8/SVneo cells: involvement of activation of focal adhesion kinase signaling.

机构信息

Laboratory of Genetic Disease and Perinatal Medicine and Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, P. R. China.

Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, P. R. China.

出版信息

PLoS One. 2014 Mar 18;9(3):e92252. doi: 10.1371/journal.pone.0092252. eCollection 2014.

Abstract

Moderate invasion of trophoblast cells into endometrium is essential for the placental development and normal pregnancy. Electric field (EF)-induced effects on cellular behaviors have been observed in many cell types. This study was to investigate the effect of physiological direct current EF (dc EF) on cellular responses such as elongation, orientation and motility of trophoblast cells. Immortalized first trimester extravillous trophoblast cells (HTR-8/SVneo) were exposed to the dc EF at physiological magnitude. Cell images were recorded and analyzed by image analyzer. Cell lysates were used to detect protein expression by Western blot. Cultured in the dc EFs the cells showed elongation, orientation and enhanced migration rate compared with non-EF stimulated cells at field strengths of 100 mV/mm to 200 mV/mm. EF exposure increased focal adhesion kinase (FAK) phosphorylation in a time-dependent manner and increased expression levels of MMP-2. Pharmacological inhibition of FAK impaired the EF-induced responses including motility and abrogated the elevation of MMP-2 expression. However, the expression levels of integrins like integrin α1, α5, αV and β1 were not affected by EF stimulation. Our results demonstrate the importance of FAK activation in migration/motility of trophobalst cells driven by EFs. In addition, it raises the feasibility of using applied EFs to promote placentation through effects on trophoblast cells.

摘要

滋养层细胞适度侵入子宫内膜对于胎盘发育和正常妊娠是必不可少的。电场(EF)对许多细胞类型的细胞行为都有影响。本研究旨在研究生理直流电 EF(dc EF)对滋养层细胞的细胞反应,如伸长、定向和运动的影响。将永生化的第一孕期绒毛外滋养层细胞(HTR-8/SVneo)暴露于生理强度的 dc EF 中。通过图像分析仪记录和分析细胞图像。用 Western blot 法检测细胞裂解物中的蛋白表达。与非 EF 刺激的细胞相比,在 100 mV/mm 至 200 mV/mm 的场强下,培养在 dc EF 中的细胞表现出伸长、定向和迁移率增强。EF 暴露以时间依赖性方式增加粘着斑激酶(FAK)磷酸化,并增加 MMP-2 的表达水平。FAK 的药理学抑制损害了 EF 诱导的反应,包括运动,并消除了 MMP-2 表达的升高。然而,EF 刺激并没有影响整合素如整合素α1、α5、αV 和β1的表达水平。我们的研究结果表明,在 EF 驱动的滋养层细胞迁移/运动中,FAK 激活是重要的。此外,它提出了通过对滋养层细胞施加应用电场来促进胎盘形成的可行性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7833/3958492/19732d4ad74e/pone.0092252.g001.jpg

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