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转录组分析揭示扩张型心肌病中自噬介导的免疫微环境调控模式。

Transcriptome analysis uncovers the autophagy-mediated regulatory patterns of the immune microenvironment in dilated cardiomyopathy.

机构信息

Department of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Hangzhou, China.

出版信息

J Cell Mol Med. 2022 Jul;26(14):4101-4112. doi: 10.1111/jcmm.17455. Epub 2022 Jun 26.

DOI:10.1111/jcmm.17455
PMID:35752958
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9279601/
Abstract

The relationship between autophagy and immunity has been well studied. However, little is known about the role of autophagy in the immune microenvironment during the progression of dilated cardiomyopathy (DCM). Therefore, this study aims to uncover the effect of autophagy on the immune microenvironment in the context of DCM. By investigating the autophagy gene expression differences between healthy donors and DCM samples, 23 dysregulated autophagy genes were identified. Using a series of bioinformatics methods, 13 DCM-related autophagy genes were screened and used to construct a risk prediction model, which can well distinguish DCM and healthy samples. Then, the connections between autophagy and immune responses including infiltrated immunocytes, immune reaction gene-sets and human leukocyte antigen (HLA) genes were systematically evaluated. In addition, two autophagy-mediated expression patterns in DCM were determined via the unsupervised consensus clustering analysis, and the immune characteristics of different patterns were revealed. In conclusion, our study revealed the strong effect of autophagy on the DCM immune microenvironment and provided new insights to understand the pathogenesis and treatment of DCM.

摘要

自噬与免疫之间的关系已经得到了很好的研究。然而,对于自噬在扩张型心肌病(DCM)进展过程中的免疫微环境中的作用,人们知之甚少。因此,本研究旨在揭示自噬在 DCM 背景下对免疫微环境的影响。通过研究健康供体和 DCM 样本之间的自噬基因表达差异,鉴定出 23 个失调的自噬基因。利用一系列生物信息学方法,筛选出 13 个与 DCM 相关的自噬基因,并构建风险预测模型,可很好地区分 DCM 和健康样本。然后,系统评估了自噬与包括浸润免疫细胞、免疫反应基因集和人类白细胞抗原(HLA)基因在内的免疫反应之间的联系。此外,通过无监督共识聚类分析确定了 DCM 中两种自噬介导的表达模式,并揭示了不同模式的免疫特征。总之,本研究揭示了自噬对 DCM 免疫微环境的强烈影响,为理解 DCM 的发病机制和治疗提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/022f/9279601/19c40851c5af/JCMM-26-4101-g003.jpg
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本文引用的文献

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Next-Generation Sequencing Reveals Novel Genetic Variants for Dilated Cardiomyopathy in Pediatric Chinese Patients.下一代测序揭示儿科中国患者扩张型心肌病的新遗传变异。
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Dilated cardiomyopathy: a new insight into the rare but common cause of heart failure.
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