Department of Obstetrics, Qingdao Women and Children's Hospital, Qingdao, 266034, PR China.
Department of Obstetrics, Qingdao Women and Children's Hospital, Qingdao, 266034, PR China.
Placenta. 2018 May;65:20-28. doi: 10.1016/j.placenta.2018.03.007. Epub 2018 Mar 28.
Preeclampsia (PE) is a hypertensive disease associated with vascular oxidative stress (OS). Besides, cell response to OS triggers growth arrest and DNA damage inducible alpha (Gadd45a). Herein, we investigated the effect of Gadd45a on OS in PE.
Umbilical cord tissues and peripheral blood samples were collected from PE patients and normal pregnant women. Immunohistochemistry was applied to identify Gadd45a level and extent of p38 phosphorylation. To verify the effect of Gadd45a on CRL1730 human umbilical vein endothelial cell (HUVEC) behavior, HUVECs were treated with hypoxia/reoxygenation (H/R) and Gadd45a-siRNA or P79350. OS products were detected using thiobarbituric acid-reactive-substance assay, immune enzyme assay, enzyme-linked immunosorbent assay (ELISA) and super oxide dismutase (SOD) kit. HUVEC behaviors were evaluated using flow cytometry, wound-healing test, and Transwell assay. The tube formation ability was assessed using in vitro tube formation assay.
PE umbilical cord tissues exhibited increased Gadd45a expression, extent of p38 phosphorylation, 8-isoprostane and oxidatively modified low density lipoprotein (Ox-LDL) and decreased SOD levels. HUVECs treated with H/R or agonist + H/R showed similar expression tendencies of related genes, enhanced apoptosis and inhibited migration, invasion, and blood vessel formation. Gadd45a-siRNA conferred alleviation to OS with decreased apoptosis, greater cell migration, invasion and blood vessel, which appeared to be weakened by treatment of Gadd45a siRNA + P79350.
Over-expression of Gadd45a and activation of the p38 MAPK signaling pathway are associated with OS in PE. Furthermore, Gadd45a knockdown promotes cell migration and invasion, and the tube formation, thus alleviating OS in PE.
子痫前期（PE）是一种与血管氧化应激（OS）相关的高血压疾病。此外，细胞对 OS 的反应会触发生长停滞和 DNA 损伤诱导的 alpha（Gadd45a）。在此，我们研究了 Gadd45a 对 PE 中 OS 的影响。
从 PE 患者和正常孕妇中采集脐带组织和外周血样本。免疫组织化学用于鉴定 Gadd45a 水平和 p38 磷酸化程度。为了验证 Gadd45a 对 CRL1730 人脐静脉内皮细胞（HUVEC）行为的影响，用缺氧/复氧（H/R）和 Gadd45a-siRNA 或 P79350 处理 HUVEC。用硫代巴比妥酸反应物质测定法、免疫酶测定法、酶联免疫吸附测定（ELISA）和超氧化物歧化酶（SOD）试剂盒检测 OS 产物。用流式细胞术、划痕试验和 Transwell 试验评估 HUVEC 行为。用体外管形成试验评估管形成能力。
PE 脐带组织表现出 Gadd45a 表达增加、p38 磷酸化程度增加、8-异前列腺素和氧化修饰的低密度脂蛋白（Ox-LDL）增加以及 SOD 水平降低。用 H/R 或激动剂+H/R 处理的 HUVEC 表现出相似的相关基因表达趋势，增强了细胞凋亡并抑制了迁移、侵袭和血管形成。Gadd45a-siRNA 减轻了 OS，降低了细胞凋亡，增加了细胞迁移、侵袭和血管形成，而用 Gadd45a-siRNA+P79350 处理则减弱了这种作用。
Gadd45a 的过度表达和 p38 MAPK 信号通路的激活与 PE 中的 OS 有关。此外，Gadd45a 敲低促进了细胞迁移和侵袭以及管形成，从而减轻了 PE 中的 OS。
