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基于液相色谱-质谱联用的系统性红斑狼疮潜在关键基因的代谢分析。

Metabolic Analysis of Potential Key Genes Associated with Systemic Lupus Erythematosus Using Liquid Chromatography-Mass Spectrometry.

机构信息

Department of Medical Cosmetology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.

出版信息

Comput Math Methods Med. 2021 Oct 4;2021:5799348. doi: 10.1155/2021/5799348. eCollection 2021.

Abstract

The biological mechanism underlying the pathogenesis of systemic lupus erythematosus (SLE) remains unclear. In this study, we found 21 proteins upregulated and 38 proteins downregulated by SLE relative to normal protein metabolism in our samples using liquid chromatography-mass spectrometry. By PPI network analysis, we identified 9 key proteins of SLE, including AHSG, VWF, IGF1, ORM2, ORM1, SERPINA1, IGF2, IGFBP3, and LEP. In addition, we identified 4569 differentially expressed metabolites in SLE sera, including 1145 reduced metabolites and 3424 induced metabolites. Bioinformatics analysis showed that protein alterations in SLE were associated with modulation of multiple immune pathways, TP53 signaling, and AMPK signaling. In addition, we found altered metabolites associated with valine, leucine, and isoleucine biosynthesis; one carbon pool by folate; tyrosine metabolism; arginine and proline metabolism; glycine, serine, and threonine metabolism; limonene and pinene degradation; tryptophan metabolism; caffeine metabolism; vitamin B6 metabolism. We also constructed differently expressed protein-metabolite network to reveal the interaction among differently expressed proteins and metabolites in SLE. A total of 481 proteins and 327 metabolites were included in this network. Although the role of altered metabolites and proteins in the diagnosis and therapy of SLE needs to be further investigated, the present study may provide new insights into the role of metabolites in SLE.

摘要

系统性红斑狼疮(SLE)发病机制的生物学机制尚不清楚。在本研究中,我们使用液相色谱-质谱法发现,与正常蛋白质代谢相比,我们的样本中 SLE 有 21 种蛋白质上调,38 种蛋白质下调。通过 PPI 网络分析,我们确定了 9 种 SLE 的关键蛋白,包括 AHSG、VWF、IGF1、ORM2、ORM1、SERPINA1、IGF2、IGFBP3 和 LEP。此外,我们在 SLE 血清中鉴定了 4569 种差异表达的代谢物,包括 1145 种减少的代谢物和 3424 种诱导的代谢物。生物信息学分析表明,SLE 中的蛋白质改变与多种免疫途径、TP53 信号和 AMPK 信号的调节有关。此外,我们发现改变的代谢物与缬氨酸、亮氨酸和异亮氨酸生物合成有关;叶酸的一碳池;酪氨酸代谢;精氨酸和脯氨酸代谢;甘氨酸、丝氨酸和苏氨酸代谢;柠檬烯和蒎烯降解;色氨酸代谢;咖啡因代谢;维生素 B6 代谢。我们还构建了差异表达蛋白-代谢物网络,以揭示 SLE 中差异表达蛋白和代谢物之间的相互作用。该网络共包含 481 种蛋白质和 327 种代谢物。虽然改变的代谢物和蛋白质在 SLE 的诊断和治疗中的作用需要进一步研究,但本研究可能为代谢物在 SLE 中的作用提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa69/8505100/928552721111/CMMM2021-5799348.001.jpg

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