Alpha-actinin-4 is essential for maintaining normal trophoblast proliferation and differentiation during early pregnancy.
Alpha-actinin-4 is essential for maintaining normal trophoblast proliferation and differentiation during early pregnancy.
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Alpha-actinin-4 对于妊娠早期维持正常滋养层增殖和分化至关重要
DOI：
10.1186/s12958-021-00733-0
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发表时间：
2021-03-23
期刊：
影响因子：
--
通讯作者：
Li Q
中科院分区：
文献类型：
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作者：
Peng W;Liu Y;Qi H;Li Q
胎盘滋养层细胞的正确分化是成功妊娠的关键，而这一过程的异常调节可能会导致不良的妊娠结局，尤其是子痫前期(Preeclampsia，PE)。然而，滋养层细胞分化的潜在机制仍不清楚。已有研究报道α-肌动蛋白-4(ACTN4)参与肌动蛋白细胞骨架的动力学和运动性。因此，我们推测ACTN4可能在妊娠早期滋养层细胞的正常增殖和分化中起重要的调节作用。为了验证这一假设，我们收集了妊娠6-10周期间接受合法终止妊娠的妇女的绒毛组织，并将它们移植到细胞培养和siRNA转染中。我们还从PE患者和健康孕妇的胎盘组织中分离出原代细胞滋养层细胞。用免疫荧光、免疫组织化学(IHC)和EDU增殖实验检测ACTN4在胎盘绒毛CTB和CTB分化为STB过程中的表达。此外，通过绒毛外植体、Matrigel侵袭实验、跨孔迁移实验和伤口愈合实验，确定ACTN4在外植体生长和细胞柱滋养层细胞(CCT)侵袭、迁移和增殖中的可能作用。Western印迹分析比较ACTN4基因敲除后绒毛或HTR8/SVneo细胞中AKT蛋白表达水平、Snail活性及上皮向间充质转化(EMT)。ACTN4在早孕绒毛CTB细胞和间质绒毛外滋养细胞(IEVT)中高表达，而在合体滋养细胞(STB)中不表达。ACTN4的下调导致滋养层细胞的增殖和外植体在体外的生长减少，以及由于肌动蛋白细丝组织的破坏而导致iEVT在体外的侵袭和迁移。这种对ACTN4的抑制也降低了AKT和Snail的活性，并进一步阻碍了EMT过程。此外，ACTN4在子痫前期胎盘iEVT中的表达下调。我们的研究结果表明，ACTN4在妊娠早期可能是滋养细胞增殖和分化的重要调节因子，该蛋白的失调可能参与了子痫前期的发病。
Proper differentiation of trophoblasts in the human placenta is essential for a successful pregnancy, whereas abnormal regulation of this process may lead to adverse pregnancy outcomes, especially preeclampsia (PE). However, the underlying mechanism of trophoblast differentiation remains unclear. Previous studies have reported the involvement of alpha-actinin-4 (ACTN4) in the actin cytoskeleton dynamics and motility. Hence, we hypothesized that ACTN4 may act as an important regulator in the normal proliferation and differentiation of trophoblasts during early pregnancy. To test this hypothesis, we collected villous tissues from women undergoing a legal pregnancy termination during 6–10 weeks of gestation and explanted them for cell culture and siRNA transfection. We also obtained placental tissues from PE patients and healthy pregnant women and isolated the primary cytotrophoblast (CTB) cells. The expression of ACTN4 in the CTBs of placental villi and during the differentiation of CTBs into STBs was detected by immunofluorescence, immunohistochemistry (IHC), and EdU proliferation assays. Besides, villous explant, Matrigel invasion, transwell migration assay, and Wound-healing assay were performed to identify the possible role of ACTN4 in the outgrowth of explants and the invasion, migration, and proliferation of cell column trophoblasts (CCTs). Western blot analysis was carried out to compare the protein expression level of AKT, Snail activities, and epithelial-to-mesenchymal transition (EMT) in the villi or HTR8/SVneo cells with ACTN4 knockdown. ACTN4 was highly expressed in CTB cells and interstitial extravillous trophoblast (iEVT) cells but not found in the syncytiotrophoblast (STB) cells in the first trimester villi. Downregulation of ACTN4 led to reduced trophoblast proliferation and explant outgrowth ex vivo, as well as iEVT invasion and migration in vitro due to disrupt of actin filaments organization. Such ACTN4 inhibition also decreased AKT and Snail activities and further impeded the EMT process. In addition, ACTN4 expression was found to be downregulated in the iEVTs from preeclamptic placentas. Our findings suggest that ACTN4 may act as an important regulator of trophoblast proliferation and differentiation during early pregnancy, and dysregulation of this protein may contribute to preeclampsia pathogenesis.
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聚 L-鸟氨酸通过促进 α-肌动蛋白 4 与肌动蛋白丝的结合来增强神经干/祖细胞的迁移。
影响因子：
4.6
作者：
Ge H;Yu A;Chen J;Yuan J;Yin Y;Duanmu W;Tan L;Yang Y;Lan C;Chen W;Feng H;Hu R
通讯作者：
Hu R
影响因子：
3.5
作者：
Mills, MA;Yang, N;North, KN
通讯作者：
North, KN
影响因子：
3.3
作者：
Medici, Damian;Hay, Elizabeth D.;Olsen, Bjorn R.
通讯作者：
Olsen, Bjorn R.
影响因子：
3.8
作者：
Horii M;Moretto-Zita M;Nelson KK;Li Y;Parast MM
通讯作者：
Parast MM
DOI：
10.1038/nrm3758
发表时间：
2014-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
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作者：
通讯作者：
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