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Transthyretin increases migration and invasion of rat placental trophoblast cells.
FEBS Open Bio ( IF 2.6 ) Pub Date : 2020-07-01 , DOI: 10.1002/2211-5463.12911
Xiao-Peng Ma 1, 2 , Chong-Dong Liu 1 , Guang-Ming Cao 1 , Zhen-Yu Zhang 1
Affiliation  

Preeclampsia (PE) is a hypertensive disorder of pregnancy. Early diagnosis of PE is currently contingent on regular prenatal physical examinations and may be facilitated by identification of novel diagnostic markers. Transthyretin (TTR), also known as prealbumin, is primarily responsible for maintaining the normal levels of thyroxine and retinol binding protein. The expression of TTR is lower in patients with severe PE as compared with healthy controls. Here, we examined the suitability of TTR as a diagnostic marker in pregnant hypertensive rats. N′‐nitro‐l‐arginine‐methylesterhydrochloride (l‐NAME) was used to generate a rat model of hypertension during pregnancy. Rat placental trophoblast cells were divided into control and TTR groups for in vitro experiments. Systolic blood pressure, diastolic blood pressure, mean blood pressure and urinary protein of hypertensive pregnant rats were higher than those of healthy pregnant rats, but these effects could be reversed by TTR treatment. There were no significant changes in blood pressure and urinary protein in healthy pregnant rats before or after TTR treatment. TTR levels in the serum and placental tissues of pregnant hypertensive rats were significantly reduced compared with those of healthy pregnant rats. Changes in placental and fetal weights in the hypertensive model could also be rescued by TTR treatment. TTR treatment significantly increased the level of matrix metalloproteinase‐2/9 in hypertensive rats. Finally, in vivo and in vitro experiments demonstrated that TTR effectively increased the migration and invasion of rat placental trophoblast cells, as well as matrix metalloproteinase‐2/9 levels in these cells. In conclusion, our data from a rat model suggest that TTR may have potential as a novel marker for PE diagnosis.

中文翻译:

转甲状腺素蛋白增加大鼠胎盘滋养层细胞的迁移和侵袭。

先兆子痫 (PE) 是妊娠期高血压疾病。PE 的早期诊断目前取决于定期的产前体检,并且可能通过识别新的诊断标志物来促进。甲状腺素运载蛋白 (TTR),也称为前白蛋白,主要负责维持甲状腺素和视黄醇结合蛋白的正常水平。与健康对照相比,重度 PE 患者的 TTR 表达较低。在这里,我们检查了 TTR 作为妊娠高血压大鼠诊断标志物的适用性。N'-硝基-l-精氨酸-甲基酯盐酸盐(l - NAME)被用于生成妊娠期高血压大鼠模型。将大鼠胎盘滋养层细胞分为对照组和 TTR 组体外实验。高血压孕鼠的收缩压、舒张压、平均血压和尿蛋白高于健康孕鼠,但这些影响可以通过TTR治疗逆转。健康孕鼠在TTR治疗前后血压和尿蛋白均无明显变化。与健康妊娠大鼠相比,妊娠高血压大鼠血清和胎盘组织中的 TTR 水平显着降低。TTR 治疗也可以挽救高血压模型中胎盘和胎儿重量的变化。TTR治疗显着增加了高血压大鼠基质金属蛋白酶2/9的水平。最后,在体内体外实验表明,TTR 有效增加了大鼠胎盘滋养层细胞的迁移和侵袭,以及这些细胞中基质金属蛋白酶 2/9 的水平。总之,我们来自大鼠模型的数据表明 TTR 可能具有作为 PE 诊断新标志物的潜力。
更新日期:2020-07-01
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