MiR-206、TGF-β1和Smad3在妊娠期高血压疾病患者胎盘组织中的表达及意义

Expression and significance of miR-206, TGF-β1 and Smad3 in placental tissue of patients with hypertensive disorders of pregnancy

摘要

目的 探讨妊娠期高血压疾病患者胎盘组织微小RNA-206(miR-206)、转化生长因子β1(TGF-β1)、Sma和Mad相关蛋白3(Smad3)的表达情况及临床意义。方法 选取2020年6月至2023年1月于河北中石油中心医院就诊的60例妊娠期高血压患者(妊娠期高血压组)、60例子痫前期患者(子痫前期组)、60例妊娠晚期健康孕妇(对照组)为研究对象.采用实时荧光定量PCR(qRT-PCR)法检测miR-206、TGF-β1和Smad3的mRNA水平,采用免疫组化法检测胎盘组织中TGF-β1和Smad3蛋白表达;采用Pearson相关分析妊娠期高血压疾病患者胎盘组织miR-206、TGF-β1 mRNA和Smad3 mRNA水平与临床资料的相关性;采用受试者工作特征(ROC)曲线分析产后胎盘组织miR-206、TGF-β1 mRNA和Smad3 mRNA水平对妊娠期高血压疾病孕妇病情的评估价值。结果 对照组、妊娠期高血压组、子痫前期组的舒张压、收缩压、24h尿蛋白、TGF-β1 mRNA、Smad3 mRNA、TGF-β1蛋白表达阳性率、Smad3蛋白表达阳性率均依次升高,清蛋白、新生儿体重、胎盘重量、miR-206均依次降低,差异有统计学意义(F/χ²值介于39.400~834.610之间,P＜0.05);妊娠期高血压疾病患者胎盘组织miR-206与收缩压、舒张压、24h尿蛋白负相关,与清蛋白、新生儿体重、胎盘重量正相关(r值介于-0.514~0.507之间,P＜0.05);TGF-β1 mRNA、Smad3 mRNA与清蛋白、新生儿体重、胎盘重量负相关,与收缩压、舒张压、24h尿蛋白正相关(r值介于-0.512~0.519之间,P＜0.05);胎盘组织miR-206、TGF-β1 mRNA和Smad3 mRNA水平单独及联合评估妊娠期高血压疾病孕妇病情的曲线下面积(AUC)分别为0.781、0.840、0.837、0.951。结论 miR-206在妊娠期高血压疾病患者胎盘组织中低表达,TGF-β1和Smad3高表达,三者可能共同参与了妊娠期高血压疾病进展.

Abstract

Objective To explore the expression and clinical significance of microRNA-206 (miR-206), transforming growth factor-β1 (TGF-β1) and Sma-and Mad-related protein 3 (Smad3) in placental tissue of patients with hypertensive disorders of pregnancy. Methods A total of 60 patients with gestational hypertension (gestational hypertension group), 60 patients with preeclampsia (preeclampsia group), and 60 healthy pregnant women in late pregnancy (control group) who were treated at Hebei PetroChina Central Hospital from June 2020 to January 2023 were selected as the study subjects. Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect the mRNA levels of miR-206, TGF-β1 and Smad3, and immunohistochemistry was used to detect the protein expressions of TGF-β1 and Smad3 in placental tissues. Pearson correlation was applied to analysis the correlation between the levels of miR-206, TGF-β1 mRNA and Smad3 mRNA levels in placental tissues and clinical data in patients with hypertensive disorders of pregnancy. Receiver operating characteristic (ROC) curves were used to analyze the value of postpartum placental tissue miR-206, TGF-β1 mRNA and Smad3 mRNA levels in assessing the condition of pregnant women with hypertensive disorders of pregnancy. Results The diastolic blood pressure, systolic blood pressure, 24-hour urine protein, TGF-β1 mRNA, Smad3 mRNA, positive expression rate of TGF-β1 protein, and positive expression rate of Smad3 protein in the control group, gestational hypertension group, and preeclampsia group increased in turn, while albumin, neonatal weight, placental weight, and miR-206 decreased sequentially, with significant differences (F/χ²=39.400-834.610, P＜0.05). In patients with gestational hypertension, miR-206 in placental tissue was negatively correlated with systolic blood pressure, diastolic blood pressure, and 24h urine protein, and positively correlated with albumin, neonatal weight, and placental weight (r=-0.514-0.507, P＜0.05). TGF-β1 mRNA and Smad3 mRNA were negatively correlated with albumin, neonatal weight and placental weight, and were positively correlated with systolic blood pressure, diastolic blood pressure, and 24h urine protein (r=-0.512-0.519, P＜0.05). The AUC of miR-206, TGF-β1 mRNA and Smad3 mRNA levels in placental tissue for alone and in combination evaluating the condition of pregnant women with hypertensive disorders were 0.781, 0.840, 0.837 and 0.951, respectively. Conclusion MiR-206 is lowly expressed in placental tissues of patients with hypertensive disorders, while TGF-β1 and Smad3 are highly expressed. The three may be involved in the progression of hypertensive disorders.

关键词

妊娠期高血压疾病 / 胎盘组织 / 微小RNA-206 / 转化生长因子β1 / Sma和Mad相关蛋白3

Key words

hypertensive disorders of pregnancy / placental tissues / microRNA-206 / transforming growth factor β1 / Sma-and Mad-related protein 3

参考文献

[1] Pop V J M, Boekhorst M G B M, Deneer R, et al. Psychological distress during pregnancy and the development of pregnancy-induced hypertension: a prospective study[J]. Psychosom Med, 2022, 84(4): 446-456.

[2] Chen B, Zhang M, He Y, et al. The association between caffeine exposure during pregnancy and risk of gestational hypertension/preeclampsia: a meta-analysis and systematical review[J]. J Obstet Gynaecol Res, 2022, 48(12): 3045-3055.

[3] Magee L A, Brown M A, Hall D R, et al. The 2021 international society for the study of hypertension in pregnancy classification, diagnosis & management recommendations for international practice[J]. Pregnancy Hypertens, 2022, 27: 148-169.

[4] Yousefzadeh Y, Soltani-Zangbar M S, Kalafi L, et al. Evaluation of CD39, CD73, HIF-1α, and their related miRNAs expression in decidua of preeclampsia cases compared to healthy pregnant women[J]. Mol Biol Rep, 2022, 49(11): 10183-10193.

[5] Huang Q K, Qiao H Y, FU M H, et al. MiR-206 Attenuates denervation-induced skeletal muscle atrophy in rats through regulation of satellite cell differentiation via TGF-β1, Smad3, and HDAC4 signaling[J]. Med Sci Monit, 2016, 22: 1161-1170.

[6] 中华医学会心血管病学分会女性心脏健康学组, 中华医学会心血管病学分会高血压学组. 妊娠期高血压疾病血压管理专家共识(2019)[J]. 中华心血管病杂志, 2020, 48(3): 195-204.

[7] Ju D H, Lee H, Ha S J. The presence of hypertension during pregnancy determines the future risk of metabolic syndrome: an observational study[J]. Medicine (Baltimore), 2022, 101(42): e31272.

[8] 戴鑫伟, 朱利平, 汪云. 子痫前期和慢性高血压并发子痫前期的临床特点及母儿结局[J]. 中国妇幼健康研究, 2022, 33(9): 64-69.

[9] Gupta S, Petras L, Tufail M U, et al. Hypertension in pregnancy: what we now know[J]. Curr Opin Nephrol Hypertens, 2023, 32(2): 153-164.

[10] Yang P Y, Tsai Y L, Chang Y J, et al. Comparisons of urine protein-to-creatinine ratios and their dynamic change patterns during labor at term between normal pregnant women and women with pregnancy induced hypertension[J]. Int J Med Sci, 2022, 19(9): 1473-1481.

[11] Mary S, Small H, Herse F, et al. Preexisting hypertension and pregnancy-induced hypertension reveal molecular differences in placental proteome in rodents[J]. Physiol Genomics, 2021, 53(6): 259-268.

[12] Wang Y, Li B, Zhao Y. Inflammation in preeclampsia: genetic biomarkers, mechanisms, and therapeutic strategies[J]. Front Immunol, 2022, 13: 883404.

[13] Li L, Li X, Zhu Y, et al. Human trophoblast cell-derived extracellular vesicles facilitate preeclampsia by transmitting miR-1273d, miR-4492, and miR-4417 to target HLA-G[J]. Reprod Sci, 2022, 29(9): 2685-2696.

[14] Shu C, Xu P, Han J, et al. Upregulation of circRNA hsa_circ_0008726 in pre-eclampsia inhibits trophoblast migration, invasion, and EMT by regulating miR-345-3p/RYBP axis[J]. Reprod Sci, 2022, 29(10): 2829-2841.

[15] 张丽, 彭静, 金璟, 等. 妊娠期高血压疾病孕妇血清和胎盘组织中血管内皮生长因子,糖基化终末产物,转化生长因子-β1表达及其与病情严重程度相关性研究[J]. 陕西医学杂志, 2022, 51(8): 953-956, 960.

[16] Qi Y, Cui S, Liu L, et al. Expression and role of miR-146a and SMAD4 in placental tissue of pregnant women with preeclampsia[J]. J Obstet Gynaecol Res, 2022, 48(8): 2151-2161.

[17] Liu E, Liu Z, Zhou Y, et al. MicroRNA-142-3p inhibits trophoblast cell migration and invasion by disrupting the TGF-β1/Smad3 signaling pathway[J]. Mol Med Rep, 2019, 19(5): 3775-3782.

[18] 龚宝兰, 黄光荣, 王任晓, 等. 妊娠期高血压患者胎盘TGF-β1及Smad的表达及意义[J]. 中华临床医师杂志(电子版), 2013, 22: 10070-10073.

[19] 陈亚玲, 贺全勤, 徐霞, 等. miR-206,HLA-G以及GATA-3在妊娠期高血压患者血清和胎盘组织中的表达及意义[J]. 广东医学, 2019, 40(18): 2623-2628.

[20] Awobajo F O, Samuel T A, Morakinyo A O, et al. Aberrant effect of genistein on placenta development expressed through alteration in transforming growth factor-β1 and alkaline phosphatase across the maternal serum, the placenta and the amniotic fluid[J]. Iran J Basic Med Sci, 2020, 23(10): 1301-1306.

基金资助

廊坊市科技支撑计划项目(2022013125)