白细胞介素-32是一种物种特异性细胞因子,在炎症中起重要作用,癌症,和其他疾病;它在生殖和妊娠相关疾病中的作用仍然未知。本研究旨在探讨白细胞介素-32在生殖和妊娠相关疾病中的作用。妊娠高血压患者的胎盘组织,健康的孕妇,并分析了滋养层系。通过聚合酶链反应和免疫组织化学定量白细胞介素-32的表达,白细胞介素-32调节后进行功能测定。白细胞介素-32仅在胎盘哺乳动物中被发现,比如食肉,牛角虫,翼翅目,皮翅目,Lagomorpa,Perissodactyla,通过生物信息学和灵长类动物。免疫组织化学和聚合酶链反应显示白细胞介素-32在人胎盘绒毛中高表达,在蜕膜和子宫内膜组织中低表达,在小鼠组织中未检测到。第二,白细胞介素-32通过增加DROSHA表达上调miR-205表达,miR-205通过靶向其启动子区促进白细胞介素-32表达。白细胞介素-32和miR-205显著增强了HTR8/SVneo细胞(滋养层细胞系)的侵袭能力和人脐静脉内皮细胞的成管能力。通过定量逆转录聚合酶链反应和免疫印迹,白细胞介素-32/miR-205环通过核因子κB信号通路增加HTR-8/SVneo细胞中MMP2和MMP9的表达.最后,使用定量逆转录聚合酶链反应,IL-32和miR-205在妊娠高血压综合征患者胎盘中的表达水平显著低于正常妊娠妇女.总之,白细胞介素-32通过miR-205-核因子κB-MMP2/9通路调节滋养细胞的侵袭,这与妊娠高血压有关。
Interleukin-32 is a species-specific cytokine that plays an important role in inflammation, cancer, and other diseases; however, its role in reproductive and pregnancy-related diseases remains unknown. This study aimed to investigate the role of interleukin-32 in reproductive and pregnancy-related diseases. Placental tissues from patients with pregnancy-induced hypertension, healthy pregnant women, and trophoblast lines were analysed. Interleukin-32 expression was quantified via polymerase chain reaction and immunohistochemistry, and functional assays were performed after interleukin-32 modulation. Interleukin-32 was identified only in placental mammals, such as Carnivora, Cetartiodactyla, Chiroptera, Dermoptera, Lagomorpha, Perissodactyla, and Primates via bioinformatics. Immunohistochemistry and polymerase chain reaction revealed that interleukin-32 was highly expressed in human placental villi, poorly expressed in decidua and endometrial tissues, and was not detected in mouse tissues. Second, interleukin-32 upregulates miR-205 expression by increasing DROSHA expression, and miR-205 promotes interleukin-32 expression by targeting its promoter region. Interleukin-32 and miR-205 significantly enhanced the invasion ability of HTR8/SVneo cells (a trophoblast cell line) and the tube formation ability of human umbilical vein endothelial cells. Through quantitative reverse transcription polymerase chain reaction and western blotting, the interleukin-32/miR-205 loop increased MMP2 and MMP9 expression in HTR-8/SVneo cells via the nuclear factor kappa B signalling pathway. Finally, using quantitative reverse transcription polymerase chain reaction, interleukin-32 and miR-205 expression levels were significantly lower in the placentas of patients with pregnancy-induced hypertension than in women with normal pregnancies. In conclusion, interleukin-32 regulates trophoblast invasion through the miR-205-nuclear factor kappa B-MMP2/9 pathway, which is involved in pregnancy-induced hypertension.