Untargeted metabolomics analysis on kidney tissues from mice reveals potential hypoxia biomarkers.

Untargeted metabolomics analysis on kidney tissues from mice reveals potential hypoxia biomarkers.
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对小鼠肾组织的非靶向代谢组学分析揭示了潜在的缺氧生物标志物。

DOI:
10.1038/s41598-023-44629-y
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发表时间:
2023-10-16
期刊:
影响因子:
4.6
通讯作者:
Nauli, Surya M.
Nauli, Surya M.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Sajid, Muhammad Imran;Nunez, Francisco J.;Amirrad, Farideh;Roosan, Moom Rahman;Vojtko, Tom;Mcculloch, Scott;Alachkar, Amal;Nauli, Surya M.

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慢性缺氧可能对心血管系统和肾脏系统产生巨大影响。显微镜技术、代谢组学和生物信息学的进步为识别新的生物标志物提供了契机。在本研究中,我们旨在通过非靶向代谢组学分析,阐明慢性缺氧诱导的肾脏组织代谢变化。采用反相超高效液相色谱 - 质谱/质谱(RP - UPLC - MS/MS)和亲水相互作用液相色谱(HILIC) - UPLC - MS/MS方法,并结合正离子和负离子模式电喷雾电离进行代谢谱分析。代谢组学分析显示,与肉碱合成和嘌呤代谢相关的代谢物增加。此外,胆红素也显著增加。同时发现,血红素、N - 乙酰 - L - 天冬氨酸、甲状腺素和3 - β - 羟基 - 5 - 胆甾烯酸酯显著下调。在雄性小鼠肾脏中,3 - β - 羟基 - 5 - 胆甾烯酸酯的下调幅度比雌性更为明显。三色染色还显示,慢性缺氧小鼠出现显著的肾纤维化。我们的研究为缺氧肾脏提供了潜在的细胞内代谢物特征。
Chronic hypoxia may have a huge impact on the cardiovascular and renal systems. Advancements in microscopy, metabolomics, and bioinformatics provide opportunities to identify new biomarkers. In this study, we aimed at elucidating the metabolic alterations in kidney tissues induced by chronic hypoxia using untargeted metabolomic analyses. Reverse phase ultrahigh performance liquid chromatography-mass spectroscopy/mass spectroscopy (RP–UPLC–MS/MS) and hydrophilic interaction liquid chromatography (HILIC)–UPLC–MS/MS methods with positive and negative ion mode electrospray ionization were used for metabolic profiling. The metabolomic profiling revealed an increase in metabolites related to carnitine synthesis and purine metabolism. Additionally, there was a notable increase in bilirubin. Heme, N-acetyl-l-aspartic acid, thyroxine, and 3-beta-Hydroxy-5-cholestenoate were found to be significantly downregulated. 3-beta-Hydroxy-5-cholestenoate was downregulated more significantly in male than female kidneys. Trichome Staining also showed remarkable kidney fibrosis in mice subjected to chronic hypoxia. Our study offers potential intracellular metabolite signatures for hypoxic kidneys.
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