Metabonomic analysis of potential biomarkers and drug targets involved in diabetic nephropathy mice.
Metabonomic analysis of potential biomarkers and drug targets involved in diabetic nephropathy mice.
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糖尿病肾病小鼠潜在生物标志物和药物靶点的代谢组学分析
DOI：
10.1038/srep11998
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发表时间：
2015-07-07
影响因子：
4.6
通讯作者：
Gao H
中科院分区：
文献类型：
--
作者：
Wei T;Zhao L;Jia J;Xia H;Du Y;Lin Q;Lin X;Ye X;Yan Z;Gao H
糖尿病肾病（DN）是糖尿病全身性微血管疾病的致死性表现之一。阐明糖尿病进展过程中的特征性代谢改变对于了解其发病机制和识别与该疾病有关的潜在生物标志物和药物靶点至关重要。本研究采用基于1H核磁共振（1H NMR）的代谢组学与相关分析方法，研究db/ dbdiabetes小鼠尿液和肾脏样本的特征代谢物及其相关途径，并与年龄匹配的野生型组进行比较。db/dbmice的时间轨迹图显示，随着肾脏损伤和功能障碍的进展，尿液代谢谱以年龄依赖的方式发生改变。年龄依赖性和相关代谢物分析发现顺式乌头酸和尿囊素可以作为诊断DN的生物标志物。进一步的相关分析表明，二甲基精氨酸二甲氨基水解酶（DDAH）、鸟苷三磷酸环水解酶I （GTPCH I）和3-羟基-3-甲基戊二酰辅酶a裂解酶（HMG-CoA裂解酶）分别参与二甲胺代谢、生酮和GTP代谢途径，可能是DN的潜在治疗靶点。我们的研究结果强调，代谢组学分析可以作为一种工具来识别潜在的生物标志物和新的治疗靶点，从而更好地了解疾病发生和发展的机制。
Diabetic nephropathy (DN) is one of the lethal manifestations of diabetic systemic microvascular disease. Elucidation of characteristic metabolic alterations during diabetic progression is critical to understand its pathogenesis and identify potential biomarkers and drug targets involved in the disease. In this study,1H nuclear magnetic resonance (1H NMR)-based metabonomics with correlative analysis was performed to study the characteristic metabolites, as well as the related pathways in urine and kidney samples ofdb/dbdiabetic mice, compared with age-matchedwildtypemice. The time trajectory plot ofdb/dbmice revealed alterations, in an age-dependent manner, in urinary metabolic profiles along with progression of renal damage and dysfunction. Age-dependent and correlated metabolite analysis identified that cis-aconitate and allantoin could serve as biomarkers for the diagnosis of DN. Further correlative analysis revealed that the enzymes dimethylarginine dimethylaminohydrolase (DDAH), guanosine triphosphate cyclohydrolase I (GTPCH I) and 3-hydroxy-3-methylglutaryl-CoA lyase (HMG-CoA lyase) were involved in dimethylamine metabolism, ketogenesis and GTP metabolism pathways, respectively and could be potential therapeutic targets for DN. Our results highlight that metabonomic analysis can be used as a tool to identify potential biomarkers and novel therapeutic targets to gain a better understanding of the mechanisms underlying the initiation and progression of diseases.
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影响因子：
2.6
作者：
Connor, SC;Hodson, MP;Haselden, JN
通讯作者：
Haselden, JN
影响因子：
3.5
作者：
Chobanyan-Juergens, Kristine;Fuchs, Anne-Jule;Luecke, Thomas
通讯作者：
Luecke, Thomas
影响因子：
1.8
作者：
Nicholson, JK;Lindon, JC;Holmes, E
通讯作者：
Holmes, E
影响因子：
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作者：
Diao, Chengfeng;Zhao, Liangcai;Gao, Hongchang
通讯作者：
Gao, Hongchang
影响因子：
3.7
作者：
Guan M;Xie L;Diao C;Wang N;Hu W;Zheng Y;Jin L;Yan Z;Gao H
通讯作者：
Gao H