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整合转录组和蛋白质组分析揭示了心脏再生的潜在靶点。

Integrated transcriptomic and proteomic analysis reveals potential targets for heart regeneration.

机构信息

Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

出版信息

Biomol Biomed. 2023 Feb 1;23(1):101-113. doi: 10.17305/bjbms.2022.7770.

DOI:10.17305/bjbms.2022.7770
PMID:35997993
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9901893/
Abstract

Research on the regenerative capacity of the neonatal heart could open new avenues for the treatment of myocardial infarction (MI). However, the mechanism of cardiac regeneration remains unclear. In the present study, we constructed a mouse model of heart regeneration and then performed transcriptomic and proteomic analyses on them. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and Gene Set Enrichment Analysis (GSEA) of differentially expressed genes (DEGs) were conducted. Western blot (WB) and qPCR analyses were used to validate the hub genes expression. As a result, gene expression at the mRNA level and protein level is not the same. We identified 3186 DEGs and 42 differentially expressed proteins (DEPs). Through functional analysis of DEGs and DEPs, we speculate that biological processes such as ubiquitination, cell cycle, and oxygen metabolism are involved in heart regeneration. Integrated transcriptomic and proteomic analysis identified 19 hub genes and Ankrd1, Gpx3, and Trim72 were screened out as potential regulators of cardiac regeneration through further expression verification. In conclusion, we combined transcriptomic and proteomic analyses to characterize the molecular features during heart regeneration in neonatal mice. Finally, Ankrd1, Gpx3, and Trim72 were identified as potential targets for heart regeneration therapy.

摘要

研究新生儿心脏的再生能力可能为心肌梗死 (MI) 的治疗开辟新途径。然而，心脏再生的机制仍不清楚。在本研究中，我们构建了心脏再生的小鼠模型，然后对其进行了转录组和蛋白质组分析。对差异表达基因 (DEGs) 进行基因本体论 (GO) 富集分析、京都基因与基因组百科全书 (KEGG) 通路富集分析和基因集富集分析 (GSEA)。采用 Western blot (WB) 和 qPCR 分析验证了关键基因的表达。结果表明，mRNA 水平和蛋白水平的基因表达并不相同。我们鉴定了 3186 个 DEGs 和 42 个差异表达蛋白 (DEP)。通过对 DEGs 和 DEPs 的功能分析，我们推测心脏再生涉及泛素化、细胞周期和氧代谢等生物学过程。整合转录组和蛋白质组分析鉴定了 19 个关键基因，并通过进一步的表达验证筛选出 Ankrd1、Gpx3 和 Trim72 作为心脏再生的潜在调节因子。总之，我们结合转录组和蛋白质组分析来描述新生小鼠心脏再生过程中的分子特征。最后，鉴定出 Ankrd1、Gpx3 和 Trim72 作为心脏再生治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e917/9901893/df1b6adb25a9/bjbms-2022-7770f10.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e917/9901893/19613f92a852/bjbms-2022-7770f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e917/9901893/2f98abefe33d/bjbms-2022-7770f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e917/9901893/bcf8f968b332/bjbms-2022-7770f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e917/9901893/9ce595d73271/bjbms-2022-7770f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e917/9901893/824fb21f4734/bjbms-2022-7770f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e917/9901893/63aa6062ac32/bjbms-2022-7770f8.jpg
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