Significances of viable synergistic autophagy-associated cathepsin B and cathepsin D (CTSB/CTSD) as potential biomarkers for sudden cardiac death.
Significances of viable synergistic autophagy-associated cathepsin B and cathepsin D (CTSB/CTSD) as potential biomarkers for sudden cardiac death.
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自噬相关组织蛋白酶B和组织蛋白酶D（CTSB/CTSD）作为心脏性猝死潜在生物标志物的意义
DOI：
10.1186/s12872-021-02040-3
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发表时间：
2021-05-08
影响因子：
2.1
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Dai J;Zhang Q;Wan C;Liu J;Zhang Q;Yu Y;Wang J
组织蛋白酶家族，包括组织蛋白酶B和组织蛋白酶D，可能影响动脉粥样硬化的整个过程。虽然冠心病（CHD）作为心源性猝死（SCD）的基础已被广泛研究，但冠心病与CTSB/D之间的关系尚不清楚。我们在r中通过limma package筛选与自噬相关的差异表达蛋白（differential expression protein, DEPs）。对于筛选后的DEPs对应的基因，我们利用各种数据库对相关DEPs进行功能富集，探讨其对疾病某一特定方面可能产生的影响。通过DAVID、metscape和GSEA对DEGs进行功能富集分析。STRING和Cytoscape获得中心基因，通过GENMANIA和Networkanalyst分析相互作用网络。Western Blot检测靶基因的蛋白表达水平。TF和miRNA预测使用Networkanalyst进行，并使用Cytoscape进行可视化。与对照组相比，冠心病组织中组织蛋白酶家族成员的表达水平上调。GO和KEGG显示，组织蛋白酶在内肽酶活性、免疫反应、溶酶体途径等方面显著富集。相关性分析显示，冠心病患者CTSB/CTSD表达与ATG4D、BNIP3呈负相关，与BCL2L1、CAPNS1、TP53呈正相关。在TF-mRNA-miRNA网络中，has-miR-24-3p和has-miR-128-3p的度较高，它们可以靶向CTSB/CTSD。我们的研究结果阐明了组织蛋白酶在冠心病诱导的SCD中的表达和调控作用，并可能进一步探讨冠心病自噬的潜在机制。
The Cathepsins family, including cathepsin B and cathepsin D, potentially affects the entire processes involved in atherosclerosis. Although coronary heart disease (CHD) has been widely studied as the basis of Sudden Cardiac Death (SCD), the relationship between CHD and CTSB/D remains unclear. We screened for differentially expressed proteins (DEPs) associated with autophagy by limma package in R. For the genes corresponding to the DEPs after screening, we used various databases to carry out functional enrichment of related DEGs to explore their possible influence on a specific aspect of the disease. Functional enrichment analysis of DEGs was performed by DAVID, Metascape and GSEA. STRING and Cytoscape were obtained the hub genes, the analysis of interaction networks through the GENMANIA and Networkanalyst. Western Blot was used to validate the protein expression level of target genes. TF and miRNA prediction were performed using Networkanalyst and visualized using Cytoscape. The expression levels of members of the cathepsin family were up regulated in CHD tissues compared with the control. GO and KEGG revealed that cathepsin was markedly enriched in endopeptidase activities, immune responses, lysosome pathways, et al. The correlation analysis showed that in patients with CHD, the CTSB/CTSD expression were negatively correlated with ATG4D and BNIP3, but positively with BCL2L1, CAPNS1, and TP53. In the TF-mRNA-miRNA network, has-miR-24-3p and has-miR-128-3p had higher degrees, CTSB/CTSD could be targeted by them. Our findings elucidated the expression and regulatory role of cathepsins in coronary heart disease induced SCD and might further explore the potential mechanisms of autophagy in CHD.
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DOI：
10.1016/j.cjca.2017.01.001
发表时间：
2017-03
期刊：
The Canadian journal of cardiology
影响因子：
--
作者：
Laffont B;Rayner KJ
通讯作者：
Rayner KJ
影响因子：
37.8
作者：
Myerburg, Robert J.;Junttila, M. Juhani
通讯作者：
Junttila, M. Juhani
影响因子：
18.2
作者：
Junbo Ge;Gang Zhao;Yingzhen Yang
通讯作者：
Yingzhen Yang
影响因子：
14.9
作者：
Huang DW;Sherman BT;Tan Q;Kir J;Liu D;Bryant D;Guo Y;Stephens R;Baseler MW;Lane HC;Lempicki RA
通讯作者：
Lempicki RA
影响因子：
3.7
作者：
Dennemaerker, Julia;Lohmueller, Tobias;Reinheckel, Thomas
通讯作者：
Reinheckel, Thomas