Department of Obstetrics and Gynaecology, The Third Affiliated Hospital of Zhengzhou University, No.7 Kangfuqian Street, Erqi District, Zhengzhou, 450052, Henan, China.
Scientific Research Department, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Biol Direct. 2024 Nov 26;19(1):121. doi: 10.1186/s13062-024-00526-6.
Preeclampsia (PE) is a severe pregnancy complication characterized by complex molecular interactions. Understanding these interactions is crucial for developing effective therapeutic strategies.
This study applies a pharmacometabolomics approach to explore the roles of miR-155 and PKG1 in PE, focusing on the regulatory influence of the NF-κB signaling pathway. Blood metabolomic profiles were analyzed, and bioinformatics tools, IHC staining, Western blot (WB) analysis, and immunofluorescence (IF) localization were employed to determine the expression and function of miR-155 and PKG1. Cell invasion, migration, proliferation, and apoptosis assays were conducted to assess miR-155's modulation of PKG1. Additionally, RT-qPCR and WB analysis elucidated NF-κB-mediated regulation mechanisms.
Our findings indicate significant metabolic alterations associated with miR-155 modulation of PKG1, with NF-κB acting as a critical upstream regulator. The study demonstrates that miR-155 affects cellular functions such as invasion, migration, proliferation, and apoptosis through PKG1 modulation. Furthermore, the NF-κB signaling pathway regulates miR-155 expression, contributing to the pathological processes of PE.
This study provides a proof of concept for using pharmacometabolomics to understand the molecular mechanisms of PE, suggesting new therapeutic targets and advancing personalized medicine approaches. These insights highlight the potential of pharmacometabolomics to complement genomic and transcriptional data in disease characterization and treatment strategies, offering new avenues for therapeutic intervention in PE.
子痫前期(PE)是一种严重的妊娠并发症,其特征是复杂的分子相互作用。了解这些相互作用对于开发有效的治疗策略至关重要。
本研究采用代谢组学方法探讨 miR-155 和 PKG1 在 PE 中的作用,重点关注 NF-κB 信号通路的调节影响。分析了血液代谢组学图谱,并使用生物信息学工具、免疫组化(IHC)染色、Western blot(WB)分析和免疫荧光(IF)定位来确定 miR-155 和 PKG1 的表达和功能。进行了细胞侵袭、迁移、增殖和凋亡测定,以评估 miR-155 对 PKG1 的调节作用。此外,RT-qPCR 和 WB 分析阐明了 NF-κB 介导的调节机制。
我们的研究结果表明,miR-155 调节 PKG1 与代谢物的显著改变有关,NF-κB 作为关键的上游调节剂。研究表明,miR-155 通过调节 PKG1 影响细胞功能,如侵袭、迁移、增殖和凋亡。此外,NF-κB 信号通路调节 miR-155 的表达,参与 PE 的病理过程。
本研究提供了使用代谢组学理解 PE 分子机制的概念验证,提出了新的治疗靶点,并推进了个性化医疗方法。这些见解强调了代谢组学在疾病特征和治疗策略中的基因组和转录组数据补充方面的潜力,为 PE 的治疗干预提供了新的途径。