Involvement of signal transducers and activators of transcription in trophoblast differentiation
Involvement of signal transducers and activators of transcription in trophoblast differentiation
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信号转导子和转录激活子参与滋养层分化
DOI：
10.1016/j.placenta.2021.01.021
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发表时间：
2021-02-01
期刊：
影响因子：
3.8
通讯作者：
Zhao, Aimin
中科院分区：
文献类型：
--
作者：
Chen, Chao;Kang, Xiaomin;Zhao, Aimin
简介：为探讨信号转导子和转录激活子（STATs）在滋养层细胞分化中的作用，采用免疫组织化学（IHC）和免疫荧光（IF）方法，对人胎盘组织中STATs的定位进行研究。细胞滋养层细胞（CTB）表达STAT 1和3，但合体滋养层细胞（STBs）没有。这两种蛋白质的染色显示从细胞柱的近端部分到远端的明显上调。STAT 5 B主要在STBs中表达，CTBs中表达较低，绒毛外成纤维细胞（EVT）中不表达。接下来，通过蛋白质印迹（WB）和定量真实的时间聚合酶链反应（qRT-PCR）测试44个胎盘样品。我们发现，随着妊娠从5周增加到10周，STAT 1和3减少，STAT 5 B增加。然后，通过流式细胞术检测，胎盘与或不与蜕膜基质细胞（DSCs）的体外共培养模型显示，与DSCs共培养的胎盘滋养层细胞中人类白细胞抗原（HLA）-G阳性率增加，伴随着p-STAT 1和3的增加以及p-STAT 5和STAT 5 B的减少。最后，通过qRT-PCR检测HTR-8/SVneo中STAT沉默后的基质金属蛋白酶（MMPs）和整合素的mRNA。STAT 1沉默降低MMP 9的表达，STAT 3沉默降低MMP 9，整合素α 6，和β 4的表达，和STAT 5 B沉默增加MMP 2和整合素β 1的expression.Discussion：不同的滋养层细胞表现出不同的STAT表达谱，这与他们的MMP和整合素的表达。DSC促进滋养细胞分化为EVT，可能是通过调节STAT表达的滋养细胞。
Introduction: To explore the involvement of signal transducers and activators of transcription (STATs) in trophoblast differentiation.Methods and results: First, the localization of STATs in human placentas was detected via immunohistochemistry (IHC) and immunofluorescence (IF). Cytotrophoblasts (CTBs) expressed both STAT1 and 3, but syncytiotrophoblasts (STBs) did not. Staining for these two proteins showed a distinct upregulation from the proximal part to the distal end of cell columns. STAT5B was mainly expressed in the STBs, low in the CTBs, and absent in the extravillous tmphoblasts (EVTs). Next, the 44 placenta samples were tested via western blot (WB) and quantitative real time polymerase chain reaction (qRT-PCR). We found a decrease in STAT1 and 3 and an increase in STAT5B as gestation increased from five to 10 weeks. Then, an in vitro co-culture model of placenta with or without decidua stromal cells (DSCs), as detected via flow cytometry, revealed an increase in the human leukocyte antigen (HLA)-G positive rate in trophoblasts from placentas co-cultured with DSCs, accompanied by an increase in p-STAT1 and 3 and a decrease in p-STAT5 and STAT5B. Finally, mRNA of matrix metalloproteinases (MMPs) and integrins after STAT silencing in HTR-8/SVneo was detected via qRT-PCR. STAT1 silencing decreased MMP9 expression, STAT3 silencing decreased MMP9, integrin alpha 6, and beta 4 expression, and STAT5B silencing increased MMP2 and integrin beta 1 expression.Discussion: Different trophoblasts showed distinct STAT expression profiles which were related to their MMP and integrin expression. DSCs promoted trophoblast differentiation into EVTs, possibly by regulating the STAT expression of the trophoblasts.