Department of Obstetrics and Gynecology, Renmin Hospital, Wuhan University, Hubei, PR China.
Department of Preventive Medicine, School of Health Science, Wuhan University, Wuhan, Hubei, PR China.
Placenta. 2020 Jan 1;89:10-19. doi: 10.1016/j.placenta.2019.10.009. Epub 2019 Oct 15.
Bioinformatics analysis indicated that the arrestin ARRDC3 was upregulated in placental tissue from patients with preeclampsia (PE). The study aimed to confirm the finding by examining placenta samples from women with and without early-onset PE and to investigate ARRDC3 roles in trophoblast function.
ARRDC3 expression level and localization in placental tissue were determined by Western blot, real-time quantitative PCR and immunohistochemistry. An in vitro hypoxia and an in vitro ischemia (hypoxia/reoxygenation) cell models were used to determine the hypoxic and ischemic effects on ARRDC3 expression in extravillous trophoblast-derived HTR/8SVneo cells and trophoblast cell activity. The role of ARRDC3 in HTR8/SVneo cell proliferation, invasion and tube formation in vitro was investigated by testing the effects of ARRDC3 gene overexpression or siRNA-based gene silencing.
ARRDC3 expression was significantly elevated in placental tissue from women with early-onset PE compared to preterm birth pregnancies. ARRDC3 protein was localized in human placental trophoblasts. Hypoxia and ischemia both enhanced ARRDC3 protein expression in HTR8/SVneo cells. Hypoxia altered trophoblast cell activities. Overexpression of ARRDC3 in HTR8/SVneo cells suppressed cell invasion and tube formation. ARRDC3 gene silencing, by contrast, promoted invasion and tube formation under hypoxic conditions.
ARRDC3 was highly expressed in placental tissues of PE patients and directly affected biological activities of trophoblasts under hypoxic conditions. In regulation of ARRDC3- protein expression, ischemia (hypoxia/reoxygenation) are also important. These findings suggest that ARRDC3 may play a clinically significant role in the pathogenesis of PE.
生物信息学分析表明， arrestin ARRDC3 在子痫前期（PE）患者胎盘组织中上调。本研究旨在通过检查患有早发性 PE 和无早发性 PE 的妇女的胎盘样本来证实这一发现，并研究 ARRDC3 在滋养细胞功能中的作用。
通过 Western blot、实时定量 PCR 和免疫组织化学检测胎盘组织中 ARRDC3 的表达水平和定位。体外缺氧和体外缺血（缺氧/复氧）细胞模型用于确定缺氧和缺血对绒毛外滋养细胞衍生的 HTR/8SVneo 细胞中 ARRDC3 表达和滋养细胞活性的影响。通过检测 ARRDC3 基因过表达或基于 siRNA 的基因沉默对 HTR8/SVneo 细胞增殖、侵袭和体外管形成的影响，研究 ARRDC3 在 HTR8/SVneo 细胞中的作用。
与早产妊娠相比，早发性 PE 妇女的胎盘组织中 ARRDC3 表达明显升高。ARRDC3 蛋白定位于人胎盘滋养细胞中。缺氧和缺血均增强了 HTR8/SVneo 细胞中 ARRDC3 蛋白的表达。缺氧改变了滋养细胞的活性。在 HTR8/SVneo 细胞中过表达 ARRDC3 抑制了细胞侵袭和管形成。相比之下，在缺氧条件下，ARRDC3 基因沉默促进了侵袭和管形成。
ARRDC3 在 PE 患者的胎盘组织中高表达，并直接影响缺氧条件下滋养细胞的生物学活性。在 ARRDC3 蛋白表达的调节中，缺血（缺氧/复氧）也很重要。这些发现表明，ARRDC3 可能在 PE 的发病机制中发挥重要的临床作用。
