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长链非编码 RNA HOXD-AS1 通过 MAPK 通路促进子痫前期进展。

LncRNA HOXD-AS1 promotes preeclampsia progression via MAPK pathway.

机构信息

Department of Obstetric, The Second People's Hospital of Liaocheng, Linqing, China.

出版信息

Eur Rev Med Pharmacol Sci. 2018 Dec;22(24):8561-8568. doi: 10.26355/eurrev_201812_16618.

DOI:10.26355/eurrev_201812_16618
PMID:30575894
Abstract

OBJECTIVE

To investigate the role of HOXD-AS1 in preeclampsia and its underlying mechanism.

PATIENTS AND METHODS

A total of 50 preeclampsia primiparas and 34 normal pregnancies admitted in our hospital from July 2015 to July 2017 were selected as the study group and control group, respectively. Age, body weight, blood pressure, 24-h urinary protein and neonatal weight were compared between the two groups. HOXD-AS1 expression in the placenta tissues was detected by quantitative Real-time PCR (qRT-PCR). Preeclampsia patients were further assigned into high and low expression group according to their HOXD-AS1 expressions. The relationship between HOXD-AS1 expression and blood pressure, 24-h urinary protein and neonatal weight in preeclampsia patients were analyzed. For in vitro experiments, transfection efficacy of pcDNA-HOXD-AS1 and si-HOXD-AS1 were detected by qRT-PCR. Proliferative and colony formation abilities in BeWo and Wish cells were detected by CCK-8 and colony formation assay, respectively. Moreover, protein expressions of p-p38, p-JNK, and p-ERK were detected by Western blot.

RESULTS

The systolic blood pressure, diastolic blood pressure and urinary protein in preeclampsia patients were higher than those of normal pregnancies. However, neonatal weight in preeclampsia patients was lower than that of normal pregnancies. HOXD-AS1 expressions were gradually increased in normal pregnancies, patients with late onset preeclampsia and patients with early onset preeclampsia sequentially. Additionally, higher levels of systolic pressure, diastolic pressure and 24-h urinary protein, as well as lower neonatal weight, were observed in preeclampsia patients with high expression of HOXD-AS1 than those with low expression. In vitro results demonstrated that proliferative and colony formation abilities in trophoblasts were elevated after HOXD-AS1 knockdown. Western blot data illustrated that protein expressions of p-p38 and p-JNK were decreased, while p-ERK expression was increased after overexpression of HOXD-AS1 in trophoblasts.

CONCLUSIONS

HOXD-AS1 participates in the development and progression of preeclampsia by regulating trophoblast proliferation via the MAPK pathway.

摘要

目的

探讨 HOXD-AS1 在子痫前期中的作用及其机制。

方法

选取 2015 年 7 月至 2017 年 7 月我院收治的 50 例初产妇子痫前期患者为研究组,34 例正常妊娠产妇为对照组。比较两组年龄、体质量、血压、24 h 尿蛋白及新生儿体质量。采用实时荧光定量 PCR(qRT-PCR)检测胎盘组织中 HOXD-AS1 的表达。根据 HOXD-AS1 的表达情况,将子痫前期患者分为高表达组和低表达组。分析子痫前期患者 HOXD-AS1 表达与血压、24 h 尿蛋白及新生儿体质量的关系。体外实验中,采用 qRT-PCR 检测 pcDNA-HOXD-AS1 和 si-HOXD-AS1 的转染效率。采用 CCK-8 法和集落形成实验检测 BeWo 细胞和 Wish 细胞的增殖和集落形成能力。采用 Western blot 检测 p-p38、p-JNK 和 p-ERK 蛋白的表达。

结果

子痫前期患者的收缩压、舒张压和尿蛋白均高于正常妊娠产妇,新生儿体质量低于正常妊娠产妇。HOXD-AS1 表达水平在正常妊娠产妇中逐渐升高,在晚发型子痫前期患者、早发型子痫前期患者中依次升高。HOXD-AS1 高表达的子痫前期患者收缩压、舒张压和 24 h 尿蛋白较高,新生儿体质量较低。体外实验结果显示,HOXD-AS1 敲低后滋养细胞的增殖和集落形成能力升高。Western blot 数据表明,HOXD-AS1 过表达后滋养细胞中 p-p38 和 p-JNK 蛋白表达降低,p-ERK 蛋白表达升高。

结论

HOXD-AS1 通过调节 MAPK 通路影响滋养细胞增殖,参与子痫前期的发生发展。

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