Decreased expression of fibroblast growth factor 13 in early-onset preeclampsia is associated with the increased trophoblast permeability
Decreased expression of fibroblast growth factor 13 in early-onset preeclampsia is associated with the increased trophoblast permeability
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早发性先兆子痫中成纤维细胞生长因子 13 表达降低与滋养层通透性增加相关
DOI：
10.1016/j.placenta.2017.12.009
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发表时间：
2018
期刊：
影响因子：
3.8
通讯作者：
Yu YH
中科院分区：
文献类型：
--
作者：
Yue XJ;Sun Y;Zhong M;Ma YL;Wei YX;Sun F;Xiao L;Liu M;Chen JN;Lai YJ;Yan CM;Huang LP;Yu YH
目的：细胞内蛋白成纤维细胞生长因子13 （FGF13）在人胎盘中高表达，但其生物学功能尚不清楚。本研究旨在探讨FGF13在早发性子痫前期（PE）胎盘中的表达及其在PE病理生理中的相关机制。方法：采用免疫荧光染色法、Western blot法和定量PCR法检测早发性PE和正常妊娠患者胎盘中FGF13的表达水平。我们在滋养细胞BeWo和HTR8/SVneo中敲除FGF13，并分析细胞通透性。应用细胞角蛋白7 （cytokeratin 7, CK7）免疫荧光染色法对人胎盘切片进行临床滋养细胞-细胞连接鉴定。在BeWo和HTR8/SVneo细胞株中调控FGF13的表达，通过逆转录、定量PCR、Western blot和免疫荧光染色检测E-cadherin的表达。FGF13和E-cadherin在离体人原代滋养细胞中的表达得到进一步证实。结果：早发性PE患者胎盘中FGF13表达下调，滋养细胞排列紊乱。在滋养细胞系中，FGF13表达降低导致细胞通透性增加，E-cadherin表达降低。从PE患者分离的人绒毛滋养细胞中进一步证实了FGF13不足介导的e -钙粘蛋白缺失。结论：早发性PE患者胎盘中FGF13表达下调。FGF13通过调节E-cadherin在维持胎盘滋养层通透性中发挥重要作用。(c) 2018 Elsevier Ltd.版权所有。
Objective: Intracellular protein fibroblast growth factor 13 (FGF13) is highly expressed in human placenta, although its biological function remains unexplored. The aims of this study were to investigate the expression of FGF13 in placentae with early-onset preeclampsia (PE) and the associated mechanisms in the pathophysiology of PE. ..Methods: The expression levels of FGF13 in placentae obtained from patients with early-onset PE and normal pregnancies were assessed using immunofluorescent staining, Western blot assays and quantitative PCR. We knocked down FGF13 in trophoblast cell lines BeWo and HTR8/SVneo, and analyzed cell permeability. Clinical trophoblast cell-cell junctions were identified by cytokeratin 7 (CK7) immunofluorescent staining of human placental sections. The expressions of FGF13 were manipulated in BeWo and HTR8/SVneo cell lines, and the expressions of E-cadherin were quantified by reverse transcription followed by quantitative PCR, Western blot assays and immunofluorescent staining. The expressions of FGF13 and E-cadherin were further confirmed in the isolated human primary trophoblasts. ..Results: Downregulation of FGF13 along with trophoblast disarrangement were found in human placentae with early-onset PE. In trophoblast cell lines decreased FGF13 expression resulted in increased cell permeability and decreased E-cadherin expression. The FGF13 insufficiency-mediated loss of E-cadherin was further confirmed in the human villous trophoblasts isolated from PE patients. ..Conclusion: FGF13 was downregulated in human placentae with early-onset PE. FGF13 played an important role in maintaining placental trophoblast permeability via the modulation of E-cadherin. (c) 2018 Elsevier Ltd. All rights reserved.