Genome-wide differential expression profiling of lncRNAs and mRNAs associated with early diabetic cardiomyopathy
Genome-wide differential expression profiling of lncRNAs and mRNAs associated with early diabetic cardiomyopathy
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与早期糖尿病心肌病相关的lncRNA和mRNA的全基因组差异表达谱
DOI：
10.1038/s41598-019-51872-9
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发表时间：
2019-10-25
影响因子：
4.6
通讯作者：
Ge, Zhi-Dong
中科院分区：
文献类型：
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作者：
Pant, Tarun;Dhanasekaran, Anuradha;Ge, Zhi-Dong
糖尿病心肌病是糖尿病患者心力衰竭和死亡的主要原因之一。临床上没有有效的方法来预防它的发展。长链非编码RNA（lncRNA）在心血管疾病中的作用日益受到重视。在此，我们研究了2型糖尿病db/db小鼠心脏lncRNA和mRNA的表达谱，有和没有早期糖尿病心肌病。我们发现db/db小鼠在6周龄时心脏肥大，心功能正常，但在20周龄时舒张功能下降。与非糖尿病和糖尿病对照组相比，20周龄db/db小鼠心脏中的LncRNA和mRNA转录物显着不同。与非糖尿病对照组相比，6周龄和20周龄db/db心脏中总共有1479个lncRNA转录物和1109个mRNA转录物异常表达。lncRNA-mRNA共表达网络分析显示，与差异表达mRNA关联最大的5个失调控lncRNA分别为BC 038927、G730013 B 05 Rik、2700054 A10 Rik、AK 089884和Daw 1。生物信息学分析表明，这5种lncRNA与心肌细胞的膜去极化、动作电位传导、心肌细胞收缩和肌动蛋白介导的心肌细胞运动密切相关。这项研究在患有和不患有早期糖尿病心肌病的2型小鼠中不同地表达lncRNA，并将BC 038927、G730013 B 05 Rik、2700054 A10 Rik、AK 089884和Daw 1鉴定为在糖尿病心肌病中具有高度显著性的核心lncRNA。
Diabetic cardiomyopathy is one of the main causes of heart failure and death in patients with diabetes. There are no effective approaches to preventing its development in the clinic. Long noncoding RNAs (lncRNA) are increasingly recognized as important molecular players in cardiovascular disease. Herein we investigated the profiling of cardiac lncRNA and mRNA expression in type 2 diabetic db/db mice with and without early diabetic cardiomyopathy. We found that db/db mice developed cardiac hypertrophy with normal cardiac function at 6 weeks of age but with a decreased diastolic function at 20 weeks of age. LncRNA and mRNA transcripts were remarkably different in 20-week-old db/db mouse hearts compared with both nondiabetic and diabetic controls. Overall 1479 lncRNA transcripts and 1109 mRNA transcripts were aberrantly expressed in 6- and 20-week-old db/db hearts compared with nondiabetic controls. The lncRNA-mRNA co-expression network analysis revealed that 5 deregulated lncRNAs having maximum connections with differentially expressed mRNAs were BC038927, G730013B05Rik, 2700054A10Rik, AK089884, and Daw1. Bioinformatics analysis revealed that these 5 lncRNAs are closely associated with membrane depolarization, action potential conduction, contraction of cardiac myocytes, and actin filament-based movement of cardiac cells. This study profiles differently expressed lncRNAs in type 2 mice with and without early diabetic cardiomyopathy and identifies BC038927, G730013B05Rik, 2700054A10Rik, AK089884, and Daw1 as the core lncRNA with high significance in diabetic cardiomyopathy.