Cardiac transcriptome profiling of diabetic Akita mice using microarray and next generation sequencing.
Cardiac transcriptome profiling of diabetic Akita mice using microarray and next generation sequencing.
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使用微阵列和下一代测序的糖尿病秋田小鼠的心脏转录组分析。
DOI：
10.1371/journal.pone.0182828
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Mishra PK
中科院分区：
文献类型：
--
作者：
Kesherwani V;Shahshahan HR;Mishra PK
虽然糖尿病(DM)会引起心肌病变并加重心力衰竭，但糖尿病心肌病/心力衰竭的潜在分子机制尚不清楚。Insulin2突变体(Ins2+/-)Akita是一种表现心脏功能障碍的T1 DM小鼠模型。然而，导致心肌病的心脏转录组水平的分子变化仍不清楚。为了了解糖尿病秋田鼠心脏的分子变化，我们使用下一代测序(NGS)和微阵列技术对Ins2+/-Akita和Ins2+/+对照组小鼠的心脏转录组进行了分析，并利用独创性通路(IPA)分析确定了差异表达基因在不同心力衰竭信号通路中的意义。首先，我们验证了12周男性糖尿病患者秋田的高血糖、心脏纤维化增加和心功能不全。然后，我们分析了心脏中的转录组水平。对秋田心脏的NGS分析显示，有137个差异表达的转录本，其中骨形态发生蛋白-10(BMP10)上调最多，毛发和分裂相关增强子(Helt)是最下调的基因。此外，还上调了12个长非编码RNA(LncRNAs)。对秋田心脏的芯片分析显示，351个差异表达的转录本中，Vmn1r180上调最多，WD重复结构域83相反链(WDR83OS)下调最多。此外，在秋田心脏，miR-101C和H19 lncRNA表达上调，而Neat1 lncRNA表达下调。在NGS和微阵列分析中，11个共同基因在秋田心脏中上调。IPA分析揭示了这些差异表达基因在涉及糖尿病心肌病的关键信号通路中的作用。我们的结果提供了一个平台，通过靶向这些基因和/或非编码RNA来启动有重点的未来研究，这些基因和/或非编码RNA在秋田心脏中差异表达，并参与糖尿病心肌病。
Although diabetes mellitus (DM) causes cardiomyopathy and exacerbates heart failure, the underlying molecular mechanisms for diabetic cardiomyopathy/heart failure are poorly understood. Insulin2 mutant (Ins2+/-) Akita is a mouse model of T1DM, which manifests cardiac dysfunction. However, molecular changes at cardiac transcriptome level that lead to cardiomyopathy remain unclear. To understand the molecular changes in the heart of diabetic Akita mice, we profiled cardiac transcriptome of Ins2+/- Akita and Ins2+/+ control mice using next generation sequencing (NGS) and microarray, and determined the implications of differentially expressed genes on various heart failure signaling pathways using Ingenuity pathway (IPA) analysis. First, we validated hyperglycemia, increased cardiac fibrosis, and cardiac dysfunction in twelve-week male diabetic Akita. Then, we analyzed the transcriptome levels in the heart. NGS analyses on Akita heart revealed 137 differentially expressed transcripts, where Bone Morphogenic Protein-10 (BMP10) was the most upregulated and hairy and enhancer of split-related (HELT) was the most downregulated gene. Moreover, twelve long non-coding RNAs (lncRNAs) were upregulated. The microarray analyses on Akita heart showed 351 differentially expressed transcripts, where vomeronasal-1 receptor-180 (Vmn1r180) was the most upregulated and WD Repeat Domain 83 Opposite Strand (WDR83OS) was the most downregulated gene. Further, miR-101c and H19 lncRNA were upregulated but Neat1 lncRNA was downregulated in Akita heart. Eleven common genes were upregulated in Akita heart in both NGS and microarray analyses. IPA analyses revealed the role of these differentially expressed genes in key signaling pathways involved in diabetic cardiomyopathy. Our results provide a platform to initiate focused future studies by targeting these genes and/or non-coding RNAs, which are differentially expressed in Akita hearts and are involved in diabetic cardiomyopathy.
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影响因子：
7.7
作者：
Bugger H;Boudina S;Hu XX;Tuinei J;Zaha VG;Theobald HA;Yun UJ;McQueen AP;Wayment B;Litwin SE;Abel ED
通讯作者：
Abel ED
DOI：
10.2147/dmso.s30968
发表时间：
2013
期刊：
Diabetes, metabolic syndrome and obesity : targets and therapy
影响因子：
--
作者：
Chavali V;Tyagi SC;Mishra PK
通讯作者：
Mishra PK
影响因子：
5.3
作者：
Aledo, R;Zschocke, J;Hegardt, FG
通讯作者：
Hegardt, FG
影响因子：
2.9
作者：
Jiao, Yuhang;Yang, Qing
通讯作者：
Yang, Qing
影响因子：
10.5
作者：
Dey BK;Pfeifer K;Dutta A
通讯作者：
Dutta A