CLDN1 regulates trophoblast apoptosis and proliferation in preeclampsia.
CLDN1 regulates trophoblast apoptosis and proliferation in preeclampsia.
复制标题
CLDN1调节先兆子痫的滋养细胞凋亡和增殖。
DOI：
10.1530/rep-20-0677
复制
发表时间：
2021-05-05
期刊：
影响因子：
--
通讯作者：
Lin Y
中科院分区：
文献类型：
--
作者：
Zhang YC;Qin XL;Ma XL;Mo HQ;Qin S;Zhang CX;Wei XW;Liu XQ;Zhang Y;Tian FJ;Lin Y
子痫前期是一种妊娠期高血压疾病；然而，对子痫前期仍知之甚少。应用生物信息学分析寻找与子痫前期发病相关的新基因，并确定CLDN1是与子痫前期患者和健康对照组比较差异表达最多的基因之一。定量逆转录聚合酶链式反应、免疫印迹和免疫组织化学检测结果显示，子痫前期患者绒毛组织中CLDN1的表达明显下调。此外，在HTR-8/SVneo细胞中，CLDN1基因的敲除导致细胞增殖抑制和诱导凋亡，而CLDN1的过表达逆转了这些作用。此外，RNA-seq分析表明，BIRC3基因可能位于CLDN1的下游，并参与细胞凋亡的调控。CLDN1基因的敲除证实了BIRC3的表达水平明显降低，并与裂解的PARP显著增加有关。有趣的是，在BIRC3过表达后，CLDN1基因敲除细胞的凋亡效应被挽救。总体而言，这些结果表明，CLDN1的减少抑制了BIRC3的表达，并增加了裂解的PARP水平，从而参与了子痫前期的发病。
Preeclampsia is a gestational hypertensive disease; however, preeclampsia remains poorly understood. Bioinformatics analysis was applied to find novel genes involved in the pathogenesis of preeclampsia and identified CLDN1 as one of the most differentially expressed genes when comparing patients with preeclampsia and healthy controls. The results of the qRT-PCR, Western blotting and immunohistochemistry experiments demonstrated that CLDN1 was significantly downregulated in the chorionic villi in samples from patients with preeclampsia. Furthermore, knockdown of CLDN1 in HTR-8/SVneo cells resulted in the inhibition of proliferation and induction of apoptosis, and overexpression of CLDN1 reversed these effects. In addition, RNA-seq assays demonstrated that the gene BIRC3 is potentially downstream of CLDN1 and is involved in the regulation of apoptosis. Knockdown of CLDN1 confirmed that the expression level of BIRC3 was obviously decreased and was associated with a significant increase in cleaved PARP. Interestingly, the apoptotic effect in CLDN1 knockdown cells was rescued after BIRC3 overexpression. Overall, these results indicate that a decrease in CLDN1 inhibits BIRC3 expression and increases cleaved PARP levels thus participating in the pathogenesis of preeclampsia.