糖尿病性心肌病发病机制的多组学研究:表观遗传和代谢谱。

IF 3 4区 医学 Q2 GENETICS & HEREDITY Epigenomics Pub Date : 2025-01-01 Epub Date: 2024-12-02 DOI:10.1080/17501911.2024.2435257
Li Zhou, Shuai Mei, Xiaozhu Ma, Qidamugai Wuyun, Ziyang Cai, Chen Chen, Hu Ding, Jiangtao Yan
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引用次数: 0

摘要

目的:糖尿病性心肌病(DbCM)是一种复杂的代谢性疾病,由于治疗的局限性,严重威胁着人类的健康。多组学方法有助于阐明其内在病理变化。方法:利用代谢组学、RNA-seq、蛋白质组学和转座酶可及染色质(ATAC-seq)分析来阐明DbCM的多维分子变化。结果:在DbCM小鼠的心脏和血浆中,代谢组学分析显示支链氨基酸(BCAAs)和脂质有显著差异。随后的RNA-seq和蛋白质组学分析显示,BCKDHB、PPM1K、Cpt1b、Fabp4、Acadm、Acadl、Acadvl、HADH、HADHA、HADHB、Eci1、Eci2、PDK4和HMGCS2等关键基因受到异常调控,导致BCAAs和脂肪酸紊乱。ATAC-seq分析通过揭示糖尿病心肌病小鼠染色质可及性的动态变化以及与基因表达模式的强烈正相关,强调了表观遗传调控的关键作用。此外,基序分析发现KLF15是DbCM的关键转录因子,调节与BCAAs代谢相关的核心基因。结论:我们的研究深入研究了代谢改变和表观遗传格局,揭示了KLF15可能是DbCM治疗干预的一个有希望的候选者。
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Multi-omics insights into the pathogenesis of diabetic cardiomyopathy: epigenetic and metabolic profiles.

Aim: Diabetic cardiomyopathy (DbCM), a complex metabolic disease, greatly threatens human health due to therapeutic limitations. Multi-omics approaches facilitate the elucidation of its intrinsic pathological changes.

Methods: Metabolomics, RNA-seq, proteomics, and assay of transposase-accessible chromatin (ATAC-seq) were utilized to elucidate multidimensional molecular alterations in DbCM.

Results: In the heart and plasma of mice with DbCM, metabolomic analysis demonstrated significant differences in branched-chain amino acids (BCAAs) and lipids. Subsequent RNA-seq and proteomics showed that the key genes, including BCKDHB, PPM1K, Cpt1b, Fabp4, Acadm, Acadl, Acadvl, HADH, HADHA, HADHB, Eci1, Eci2, PDK4, and HMGCS2, were aberrantly regulated, contributing to the disorder of BCAAs and fatty acids. ATAC-seq analysis underscored the pivotal role of epigenetic regulation by revealing dynamic shifts in chromatin accessibility and a robust positive correlation with gene expression patterns in diabetic cardiomyopathy mice. Furthermore, motif analysis identified that KLF15 as a critical transcription factor in DbCM, regulating the core genes implicated with BCAAs metabolism.

Conclusion: Our research delved into the metabolic alterations and epigenetic landscape and revealed that KLF15 may be a promising candidate for therapeutic intervention in DbCM.

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来源期刊
Epigenomics
Epigenomics GENETICS & HEREDITY-
CiteScore
5.80
自引率
2.60%
发文量
95
审稿时长
>12 weeks
期刊介绍: Epigenomics provides the forum to address the rapidly progressing research developments in this ever-expanding field; to report on the major challenges ahead and critical advances that are propelling the science forward. The journal delivers this information in concise, at-a-glance article formats – invaluable to a time constrained community. Substantial developments in our current knowledge and understanding of genomics and epigenetics are constantly being made, yet this field is still in its infancy. Epigenomics provides a critical overview of the latest and most significant advances as they unfold and explores their potential application in the clinical setting.
期刊最新文献
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