Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
J Reprod Immunol. 2021 Jun;145:103317. doi: 10.1016/j.jri.2021.103317. Epub 2021 Mar 30.
Alongside many complications in understanding the etiology of Preeclampsia (PE), several determinants, such as the imbalanced proportion of anti-angiogenic/proangiogenic T-cell subsets, especially CD4 (Th17/Treg), as well as alterations in the expression profile of related cytokines, miRNAs, and transcription factors might have been implicated in PE pathogenesis.
After sample collection and preparation, CD4 cells were isolated from PE and non-PE pregnant woman and were cultured. Furthermore, analysis such as flow cytometry, real-time PCR, western blotting, and ELISA were performed to assess determinants related to PE manifestation, including sFlt-1, sEng, STAT-3, RORγt, SMAD-7, Foxp3, IL-17, IL-22, Ets-1, and miRNA-326.
Our results showed that the miRNA-326 expression level increased in CD4 Cells and Th17 in PE patients which downregulated Ets-1 expression that acts as a negative control for Th17 development. Furthermore, we showed that the number and expression level of Th17 s and transcription factor RORγt escalated, respectively. While Treg and its related transcription factor (Foxp3) demonstrated a decrease. Flow cytometry analysis illustrated that the Th17/Treg ratio increased in PE. Additionally, we demonstrated that expression and concentration levels of cytokines (IL-17 and IL22) and anti-angiogenic molecules (sEng and sFlt-1) soared in isolated CD4 cells from PE patients, which could be correlated with PE pathogenicity.
In conclusion, we comprehensively evaluated immunological factors and molecules involved in PE manifestation. Interestingly, the CD4 T-cell subset could be an extra source of antiangiogenic factors for the maintenance of this hypertension disorder.
除了在理解先兆子痫（PE）病因方面存在许多并发症外，一些决定因素，如抗血管生成/促血管生成 T 细胞亚群（尤其是 CD4（Th17/Treg））的比例失衡，以及相关细胞因子、miRNA 和转录因子表达谱的改变，可能与 PE 发病机制有关。
采集和准备样本后，从 PE 和非 PE 孕妇中分离 CD4 细胞并进行培养。此外，通过流式细胞术、实时 PCR、western blot 和 ELISA 等方法分析与 PE 表现相关的决定因素，包括 sFlt-1、sEng、STAT-3、RORγt、SMAD-7、Foxp3、IL-17、IL-22、Ets-1 和 miRNA-326。
我们的结果表明，PE 患者 CD4 细胞和 Th17 中的 miRNA-326 表达水平增加，下调了 Th17 发育的负调控因子 Ets-1 的表达。此外，我们还发现 Th17 细胞的数量和表达水平分别增加，而 Treg 及其相关转录因子（Foxp3）则减少。流式细胞术分析表明，PE 患者 Th17/Treg 比值增加。此外，我们还表明，从 PE 患者分离的 CD4 细胞中细胞因子（IL-17 和 IL22）和抗血管生成分子（sEng 和 sFlt-1）的表达和浓度水平升高，这与 PE 的发病机制有关。
总之，我们全面评估了与 PE 表现相关的免疫因素和分子。有趣的是，CD4 T 细胞亚群可能是维持这种高血压疾病的抗血管生成因子的另一个来源。
