去铁胺解决代谢失调和尿路感染在体重相关妊娠糖尿病。

IF 3.4 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Min Zhang, Na Wei, Rong Lin, Yue Xu, Qingfu Zhang, Lina Jia, Xiaotong Zhang, Xiaojing Yang
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引用次数: 0

摘要

背景:妊娠期糖尿病(GDM)的患病率日益增加,特别是在超重或肥胖个体中,对健康构成了重大威胁。过量的铁有助于GDM的氧化应激、炎症和免疫和代谢功能的破坏。去铁胺(DFO)是一种铁螯合剂,可以通过恢复免疫和代谢平衡提供治疗解决方案。方法:利用GEO转录组学数据进行综合多组学分析,应用加权基因共表达网络分析(WGCNA)和基因集富集分析鉴定关键免疫代谢基因。使用AutoDock Vina进行与DFO的分子对接实验,并在PyMOL中可视化相互作用。在高糖条件下,通过cck -8、qRT-PCR、Western blot、免疫荧光、ELISA和集落形成试验等多种体外实验来评估DFO的作用,重点关注LAMA3和PI3K/AKT信号通路。结果:CDR2L、LIMCH1、LDLR、LAMA3等关键基因在妊娠期糖尿病(GDM)中存在异常调控。DFO对这些靶标表现出明显的亲和力,尤其是LDLR。在功能上,DFO被发现可以提高高血糖应激时的细胞存活率,减轻氧化应激,降低炎症细胞因子如IL-6、IL-17和IL-23的浓度。值得注意的是,沉默或阻断LAMA3可逆转这些作用,抑制PI3K/AKT通路,增加凋亡标志物,降低细胞增殖。结论:DFO通过解决铁过量和免疫代谢失调,有可能成为与肥胖相关的GDM的靶向治疗方法。LAMA3通过PI3K/AKT通路介导DFO的抗炎和促生存作用。DFO对GDM的治疗潜力有待进一步的临床研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Deferoxamine addresses metabolic dysregulation and urinary tract infections in weight-associated gestational diabetes mellitus.

Background: The increasing prevalence of gestational diabetes mellitus (GDM), particularly among overweight or obese individuals, poses significant health risks. Excess iron contributes to oxidative stress, inflammation, and disruptions in immune and metabolic functions in GDM. Deferoxamine (DFO), an iron chelator, may offer a therapeutic solution by restoring immune and metabolic balance.

Methods: We conducted a comprehensive multi-omics analysis using GEO transcriptomic data, applying Weighted Gene Co-expression Network Analysis (WGCNA) and gene set enrichment analysis to identify key immune-metabolic genes. Molecular docking experiments with DFO were performed using AutoDock Vina, and interactions were visualized in PyMOL. Various in vitro assays-CCK-8, qRT-PCR, Western blot, immunofluorescence, ELISA, and colony formation tests-were conducted under high glucose conditions to assess the effects of DFO, focusing on LAMA3 and the PI3K/AKT signaling pathway.

Results: Key genes such as CDR2L, LIMCH1, LDLR, and LAMA3 were identified as being improperly regulated in cases of gestational diabetes mellitus (GDM). DFO demonstrated a significant affinity for these targets, especially LDLR. Functionally, DFO was found to improve cell survival during hyperglycemic stress, mitigate oxidative stress, and lower the concentrations of inflammatory cytokines like IL-6, IL-17, and IL-23. Notably, silencing or blocking LAMA3 reversed these effects, inhibiting the PI3K/AKT pathway, increasing apoptosis markers, and decreasing cell proliferation.

Conclusions: DFO holds potential as a targeted treatment for GDM associated with obesity by addressing iron excess and immune-metabolic dysregulation. LAMA3 plays a crucial role in mediating DFO's anti-inflammatory and survival-promoting effects via the PI3K/AKT pathway. Further clinical studies are needed to explore DFO's therapeutic potential in GDM.

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来源期刊
European Journal of Medical Research
European Journal of Medical Research 医学-医学:研究与实验
CiteScore
3.20
自引率
0.00%
发文量
247
审稿时长
>12 weeks
期刊介绍: European Journal of Medical Research publishes translational and clinical research of international interest across all medical disciplines, enabling clinicians and other researchers to learn about developments and innovations within these disciplines and across the boundaries between disciplines. The journal publishes high quality research and reviews and aims to ensure that the results of all well-conducted research are published, regardless of their outcome.
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