Trophoblastic proliferation and invasion regulated by ACTN4 is impaired in early onset preeclampsia
Trophoblastic proliferation and invasion regulated by ACTN4 is impaired in early onset preeclampsia
复制标题
早发性先兆子痫中由 ACTN4 调节的滋养层细胞增殖和侵袭受损
DOI：
10.1096/fj.201802058rr
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发表时间：
2019-05-01
期刊：
影响因子：
4.8
通讯作者：
Baker, Philip N.
中科院分区：
文献类型：
--
作者：
Peng, Wei;Tong, Chao;Baker, Philip N.
成功妊娠需要正常的胎盘，这在很大程度上取决于对滋养细胞增殖、侵袭和迁移的严格调控。滋养细胞功能异常可导致子宫螺旋动脉重构失败，这可能与妊娠相关疾病，如先兆子痫有关。在这里，我们报道了一种肌动蛋白结合蛋白α -肌动蛋白（ACTN）4在早发性子痫前期胎盘中出现失调。此外，敲低ACTN4可通过减少AKT膜易位显著抑制滋养细胞增殖。此外，E‐cadherin调节ACTN4和β‐catenin在滋养细胞足小体上的共定位，而ACTN4的下调抑制了E‐cadherin通过解聚肌动蛋白丝诱导的细胞侵袭增加。此外，ACTN4的缺失重现了人类子痫前期的一些特征。因此，我们的数据表明，ACNT4在滋养细胞功能中发挥作用，是胎盘正常发育所必需的。-彭文伟，童春华，李丽丽，黄春华，冉艳，陈晓华，白，燕，刘玉燕，赵建军，谭，波，罗晓霞，王海华，文，丽，张春华，张海华，丁艳，齐，华，贝克，彭宁。ACTN4调控的滋养细胞增殖和侵袭在早发性子痫前期受损。中国生物医学工程学报，33,(2019):627 - 638。www.fasebj.org
Successful pregnancy requires normal placentation, which largely depends on the tight regulation of proliferation, invasion, and migration of trophoblast cells. Abnormal functioning of trophoblast cells may cause failure of uterine spiral artery remodeling, which may be related to pregnancy‐related disorders, such as preeclampsia. Here, we reported that an actin‐binding protein, α‐actinin (ACTN)4, was dysregulated in placentas from early onset preeclampsia. Moreover, knockdown of ACTN4 markedly inhibited trophoblast cell proliferation by reducing AKT membrane translocation. Furthermore, E‐cadherin regulated ACTN4 and β‐catenin colocalization on trophoblast cell podosomes, and ACTN4 down‐regulation suppressed the E‐cadherin‐induced cell invasion increase via depolymerizing actin filaments. Moreover, loss of ACTN4 recapitulated a number of the features of human preeclampsia. Therefore, our data indicate that ACNT4 plays a role in trophoblast function and is required for normal placental development.—Peng, W., Tong, C., Li, L., Huang, C., Ran, Y., Chen, X., Bai, Y., Liu, Y., Zhao, J., Tan, B., Luo, X., Wang, H., Wen, L., Zhang, C., Zhang, H., Ding, Y., Qi, H., Baker, P. N. Trophoblastic proliferation and invasion regulated by ACTN4 is impaired in early onset preeclampsia. FASEB J. 33, 6327–6338 (2019). www.fasebj.org