Overexpression of Long Noncoding RNA Uc.187 Induces Preeclampsia-Like Symptoms in Pregnancy Rats
Overexpression of Long Noncoding RNA Uc.187 Induces Preeclampsia-Like Symptoms in Pregnancy Rats
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长非编码 RNA Uc.187 的过表达会诱导妊娠大鼠出现先兆子痫样症状
DOI：
10.1093/ajh/hpaa011
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发表时间：
2020-05-01
影响因子：
3.2
通讯作者：
Jia, Ruizhe
中科院分区：
文献类型：
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作者：
Huang, Jin;Qian, Yating;Jia, Ruizhe
背景子痫前期（preeclampsia，PE）是一种严重的妊娠特异性疾病，其特征是滋养层浸润不足和胎盘植入浅。长的非编码RNA uc.187，这是从一个超保守的区域转录，在PE患者的胎盘组织中高度表达，与异常滋养层浸润。因此，本研究旨在通过体外实验研究进一步阐明uc.187与PE的关系，寻找治疗PE的新靶点。方法本研究通过建立脂多糖诱导的PE大鼠模型，进行uc.187过表达实验，并利用HTR-8/SVneo细胞进行实验，结果发现uc.187在PE大鼠胎盘中表达升高。通过给怀孕的大鼠注射含有lncRNA uc.187的慢病毒，我们成功地引发了母亲的高血压沿着一系列与人类PE相似的症状。体外实验表明，高水平的uc.187导致滋养层细胞侵袭减少。此外，我们的研究结果显示，uc.187在PE和胎儿生长受限细胞中有高表达，但在胎盘部位滋养细胞肿瘤中的表达较低。Western blot和细胞免疫荧光结果显示，HTR-8/SVneo细胞的异常生物学行为与β-catenin在细胞质和细胞核中的分布有关。uc.187的过表达可通过影响β-连环蛋白在细胞质和细胞核中的分布而在妊娠大鼠模型中诱导PE样症状。
BACKGROUNDAs a serious pregnancy-specific condition, preeclampsia (PE) is a serious pregnancy-specific condition characterized by insufficient trophoblastic invasion and shallow placental implantation. Long noncoding RNA uc.187, which is transcribed from an ultra-conserved region is highly expressed in the placental tissue of patients with PE, is associated with abnormal trophoblast invasion. Therefore, we aimed to further characterize the relationship between uc.187 and PE through in vitro experimental studies to find new targets to treat PE.METHODSIn this study, we constructed PE rat models induced by lipopolysaccharide, experimented with overexpressing uc.187 and performed experiments using HTR-8/SVneo cells.RESULTSWe found uc.187 was elevated in the placenta of PE rats. By injecting pregnant rats with a lentivirus containing the lncRNA uc.187, we successfully triggered maternal hypertension along with a series of symptoms similar to PE in humans. In vitro experiments demonstrated that high levels of uc.187 lead to decreased trophoblast invasion. In addition, our results revealed that uc.187 had high expression in PE and fetal growth restricted cells, but low expression in placental site trophoblastic tumors compared with the control groups. Results of western blot and cell immunofluorescence indicated that the aberrant biological behavior of HTR-8/SVneo cells were related to the distribution of beta-catenin in the cytoplasm and nucleus.CONCLUSIONSTaken together, our study revealed that uc.187 was negatively correlated to trophoblastic cell invasion, and overexpression of uc.187 could induce PE-like symptoms in a pregnant rat model by affecting the distribution of beta-catenin in the cytoplasm and nucleus.