Changes in N6-Methyladenosine Modification Modulate Diabetic Cardiomyopathy by Reducing Myocardial Fibrosis and Myocyte Hypertrophy.
Changes in N6-Methyladenosine Modification Modulate Diabetic Cardiomyopathy by Reducing Myocardial Fibrosis and Myocyte Hypertrophy.
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DOI：
10.3389/fcell.2021.702579
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发表时间：
2021
影响因子：
5.5
通讯作者：
Wu J
中科院分区：
文献类型：
--
作者：
Ju W;Liu K;Ouyang S;Liu Z;He F;Wu J
在本研究中，我们旨在系统地分析糖尿病心肌病（DCM）小鼠模型中总RNA N6-甲基腺苷（m6 A）修饰模式。通过m6 A特异性甲基化RNA免疫沉淀，然后进行高通量测序（MeRIP-seq）和RNA测序（RNA-seq），分析DCM和正常心脏中m6 A的模式。通过对DCM和正常心脏的输入和m6 A免疫沉淀RNA样品进行定量实时PCR分析，验证m6 A相关mRNA。在DCM样品中共检测到973个新的m6 A峰，并选择984个差异甲基化位点进行进一步研究，包括295个高甲基化和689个低甲基化m6 A位点（倍数变化（FC）> 1.5，P < 0.05）。基因本体论（GO）和京都基因和基因组百科全书（KEGG）通路分析表明，DCM中独特的m6 A修饰转录本与心脏纤维化、心肌肥大和心肌能量代谢密切相关。DCM中总m6 A水平较高，而脂肪量和肥胖相关（FTO）蛋白水平下调。在DCM模型小鼠中过表达FTO通过减少心肌纤维化和心肌细胞肥大改善心功能。总体而言，m6 A修饰模式在扩张型心肌病中发生了改变，并且表观转录过程（例如m6 A）的修饰是一种潜在的有趣治疗方法。
In this study, we aimed to systematically profile global RNA N6-methyladenosine (m6A) modification patterns in a mouse model of diabetic cardiomyopathy (DCM). Patterns of m6A in DCM and normal hearts were analyzed via m6A-specific methylated RNA immunoprecipitation followed by high-throughput sequencing (MeRIP-seq) and RNA sequencing (RNA-seq). m6A-related mRNAs were validated by quantitative real-time PCR analysis of input and m6A immunoprecipitated RNA samples from DCM and normal hearts. A total of 973 new m6A peaks were detected in DCM samples and 984 differentially methylated sites were selected for further study, including 295 hypermethylated and 689 hypomethylated m6A sites (fold change (FC) > 1.5, P < 0.05). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analyses indicated that unique m6A-modified transcripts in DCM were closely linked to cardiac fibrosis, myocardial hypertrophy, and myocardial energy metabolism. Total m6A levels were higher in DCM, while levels of the fat mass and obesity-associated (FTO) protein were downregulated. Overexpression of FTO in DCM model mice improved cardiac function by reducing myocardial fibrosis and myocyte hypertrophy. Overall, m6A modification patterns were altered in DCM, and modification of epitranscriptomic processes, such as m6A, is a potentially interesting therapeutic approach.
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影响因子：
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