Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
Mol Biol Rep. 2022 Nov;49(11):10183-10193. doi: 10.1007/s11033-022-07887-z. Epub 2022 Sep 1.
The Preeclampsia (PE) molecular mechanisms are not fully revealed and different biological processes are involved in the pathogenesis of PE. We aimed to evaluate adenosine and hypoxia-related signaling molecules in PE patients in the current study.
Decidua tissue and peripheral blood samples were taken from 25 healthy pregnant and 25 PE women at delivery time. CD39, CD73, and Hypoxia-inducible factor-alpha (HIF-α) were evaluated in mRNA and protein level using real-time PCR and western blotting techniques, respectively. Also, miR-30a, miR-206, and miR-18a expression were evaluated by real-time PCR. At last, secretion levels of IGF and TGF-β in the taken serum of blood samples were measured by ELISA.
Our results revealed that Expression of CD39 is decreased in PE cases versus healthy controls at mRNA and protein levels (p = 0.0003 for both). CD73 and HIF-α showed an increased level of expression in PE patients at RNA and protein status (p = 0.0157 and p < 0.0001 for protein evaluation of CD73 and HIF-α, respectively). The miRNA-30a (p = 0.0037) and miR-206 (p = 0.0113) showed elevated expression in the decidua of the PE group. The concentration of secreted IGF-1 (p = 0.0002) and TGF-β (p = 0.0101) in serum samples of PE cases compared to the healthy group were decreased.
In conclusion, our results showed that aberrant expression of molecules that are involved in ATP catabolism and the hypoxic conditions is observed in PE cases and involved in their hypertension and inflammation could be served as PE prognosis by more confirming in comprehensive future studies. miR-206 and miR-30a play a role by regulating CD39 and CD73 as molecules that are involved in ATP catabolism as well as regulating the production of IGF-1 in the process of hypertension, which is the main feature in patients with preeclampsia. On the other hand, decreased level of miR-18a lead to upregulation of HIF-1a, and the consequence condition of hypoxia increases hypertension and inflammation in these patients.
子痫前期（PE）的分子机制尚未完全揭示，不同的生物学过程参与了 PE 的发病机制。本研究旨在评估 PE 患者中腺苷和缺氧相关信号分子。
在分娩时，从 25 名健康孕妇和 25 名 PE 妇女中采集蜕膜组织和外周血样本。使用实时 PCR 和 Western 印迹技术分别评估 CD39、CD73 和缺氧诱导因子-α（HIF-α）的 mRNA 和蛋白水平。还通过实时 PCR 评估 miR-30a、miR-206 和 miR-18a 的表达。最后，通过 ELISA 测量取自血液样本的血清中 IGF 和 TGF-β 的分泌水平。
我们的结果表明，与健康对照组相比，PE 病例中 CD39 的表达在 mRNA 和蛋白水平上均降低（p=0.0003）。PE 患者的 CD73 和 HIF-α在 RNA 和蛋白状态下表达水平升高（p=0.0157 和 p<0.0001 分别用于 CD73 和 HIF-α的蛋白评估）。miR-30a（p=0.0037）和 miR-206（p=0.0113）在 PE 组的蜕膜中表达升高。与健康组相比，PE 病例血清样本中分泌的 IGF-1（p=0.0002）和 TGF-β（p=0.0101）浓度降低。
总之，我们的结果表明，在 PE 病例中观察到参与 ATP 分解代谢和缺氧条件的分子的异常表达，并参与其高血压和炎症，可通过进一步在综合未来研究中证实，作为 PE 的预后指标。miR-206 和 miR-30a 通过调节参与 ATP 分解代谢的分子 CD39 和 CD73 以及调节高血压过程中 IGF-1 的产生来发挥作用，这是子痫前期患者的主要特征。另一方面，miR-18a 水平降低导致 HIF-1a 的上调，而缺氧的后果条件会增加这些患者的高血压和炎症。
