Identification and Analysis of Hub Genes in Diabetic Cardiomyopathy: Potential Role of Cytochrome P450 1A1 in Mitochondrial Metabolism and STZ-Induced Myocardial Dysfunction.
Identification and Analysis of Hub Genes in Diabetic Cardiomyopathy: Potential Role of Cytochrome P450 1A1 in Mitochondrial Metabolism and STZ-Induced Myocardial Dysfunction.
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糖尿病心肌病 Hub 基因的鉴定和分析：细胞色素 P450 1A1 在线粒体代谢和 STZ 诱导的心肌功能障碍中的潜在作用
DOI：
10.3389/fcvm.2022.835244
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发表时间：
2022
影响因子：
3.6
通讯作者：
Guo R
中科院分区：
文献类型：
--
作者：
Chen Y;Yang J;Wang Y;Shen W;Liu J;Yuan M;Hao X;Zhong L;Guo R
糖尿病心肌病（DCM）是糖尿病患者死亡的主要原因；但其分子机制尚不清楚，也无统一的诊断标准。本研究的目的是通过筛选和分析DCM心室差异表达基因（DEG），发现DCM的发病机制和潜在的治疗靶点，并验证关键枢纽基因在DCM引起的心肌功能障碍中的作用。数据集 GSE4745 和 GSE6880 是从 GEO 数据库下载的。利用R语言、python脚本和生物信息学软件进行差异分析、可视化分析、聚类分析和富集分析，构建蛋白质-蛋白质相互作用（PPI）网络，获得hub基因。通过给雄性小鼠注射链脲佐菌素(STZ)建立DCM模型。通过超声心动图和实时定量聚合酶链反应（RT-qPCR）检查心脏功能和枢纽基因的表达，然后进行多重统计分析。生物信息学结果表明线粒体功能障碍、脂质代谢紊乱和胶原蛋白合成减少是 DCM 发生的主要原因。特别是编码细胞色素P450 1A1 (CYP4501A1)酶的枢纽基因Cyp1a1在相互作用网络中具有最高的连接性，并且与线粒体稳态和能量代谢相关。它在内源或外源底物的氧化中起着关键作用。我们的 RT-qPCR 结果证实，与正常对照相比，DCM 模型中心室 Cyp1a1 mRNA 水平上调近 12 倍，这与糖尿病个体的心功能异常相关。糖尿病心脏中线粒体中 CYP4501A1 蛋白的表达也增加。然而，我们发现患有 DCM 的小鼠心室中胶原蛋白的表达没有显着变化。该研究为理解DCM的发病机制提供了紧凑的数据支持。 CYP4501A1 可能被视为 DCM 治疗的潜在候选靶点。后续动物和临床验证需要进一步探索。
Diabetic cardiomyopathy (DCM) is a primary cause of death in diabetic patients; however, its molecular mechanism is not yet clear, and there is no uniform standard for diagnosis. The aim of this study is to discover the pathogenesis and potential therapeutic targets of DCM through screening and analysis of differentially expressed genes (DEGs) in heart ventricles of DCM, and to testify the role of key hub genes in DCM-induced myocardial dysfunction. Datasets GSE4745 and GSE6880 were downloaded from the GEO database. The difference analysis, visual analysis, cluster analysis and enrichment analysis were performed by using R language, python scripts and bioinformatics software followed by the construction of protein-protein interaction (PPI) network to obtain hub genes. The DCM models were established by streptozocin (STZ) injection to the male mice. The cardiac function and the expressions of hub genes were examined by using echocardiography and real-time quantitative poly-merase chain reaction (RT-qPCR), followed by multiple statistical analyses. Bioinformatic results indicate that mitochondrial dysfunction, disturbed lipid metabolism and decreased collagen synthesis are the main causes of the DCM development. In particular, the hub gene Cyp1a1 that encodes Cytochrome P450 1A1 (CYP4501A1) enzyme has the highest connectivity in the interaction network, and is associated with mitochondrial homeostasis and energy metabolism. It plays a critical role in the oxidation of endogenous or exogenous substrates. Our RT-qPCR results confirmed that ventricular Cyp1a1 mRNA level was nearly 12-fold upregulated in DCM model compared to normal control, which was correlated with abnormal cardiac function in diabetic individuals. CYP4501A1 protein expression in mitochondria was also increased in diabetic hearts. However, we found no significant changes in collagen expressions in cardiac ventricles of mice with DCM. This study provided compact data support for understanding the pathogenesis of DCM. CYP4501A1 might be considered as a potential candidate targeting for DCM therapy. Follow-up animal and clinical verifications need to be further explored.
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影响因子：
4.8
作者：
Granéli C;Hicks R;Brolén G;Synnergren J;Sartipy P
通讯作者：
Sartipy P
DOI：
10.1073/pnas.1414126111
发表时间：
2014-12-09
影响因子：
11.1
作者：
Aguda, Adeleke H.;Panwar, Preety;Broemme, Dieter
通讯作者：
Broemme, Dieter
影响因子：
4.6
作者：
Guo R;Hua Y;Rogers O;Brown TE;Ren J;Nair S
通讯作者：
Nair S
影响因子：
4.8
作者：
Dasari, Venkata Ramesh;Anandatheerthavarada, Hindupur K.;Avadhani, Narayan G.
通讯作者：
Avadhani, Narayan G.
DOI：
10.1111/j.1742-4658.2011.08356.x
发表时间：
2011-11
期刊：
The FEBS journal
影响因子：
--
作者：
Avadhani NG;Sangar MC;Bansal S;Bajpai P
通讯作者：
Bajpai P