Background

Structural remodeling plays an important role in the occurrence and maintenance of atrial fibrillation (AF), but the mechanism is currently unclear. This study was designed to investigate the transcriptomic mechanism of structural remodeling of AF through bioinformatic analysis and in vivo and vitro experiments.

Methods

Transcriptomic datasets were retrieved from the Gene Expression Omnibus (GEO) database, and bioinformatics analysis was performed to screen mRNAs associated with AF. Cell and animal models were constructed to verify the bioinformatic findings using RT-qPCR and western blot analysis. Then, SPP1 was screened as the target gene, and the mechanism by which it promotes fibrosis was further studied in human cardiac fibroblasts (HCFs) using western blot analysis.

Results

After retrieval, the GSE14975, GSE31821, GSE79768, GSE115574 and GSE128188 datasets were used in this study. In total, 147 differentially expressed genes (DEGs) were identified in left atrial appendix tissue and 85 in right atrial appendix tissue. According to the enrichment analysis results, the calcium signaling pathway was found to play an important role in AF, in which EGFR, AGTR1, HTR2B, CD38 and BDKRB1 might be the key genes. Moreover, SPP1 was identified as a key driver through PPI analysis and experimentally proved to reduce the expression of p27 by regulating the PI3K/Akt signaling pathway, sequentially promoting HCF fibrosis.

Conclusion

Bioinformatics analysis showed that the calcium signaling pathway might play an important role in AF, while SPP1 could promote myocardial fibrosis through the PI3K/Akt/p27 signaling axis.

中文翻译：

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心房颤动心耳中差异表达基因的多样性：SPP1在心房纤维化中的作用和机制

背景

结构重构在心房颤动（AF）的发生和维持中起重要作用，但其机制目前尚不清楚。本研究旨在通过生物信息学分析和体内外实验研究 AF 结构重塑的转录组学机制。

方法

从基因表达综合 (GEO) 数据库中检索转录组数据集，并进行生物信息学分析以筛选与 AF 相关的 mRNA。构建细胞和动物模型以使用 RT-qPCR 和蛋白质印迹分析验证生物信息学发现。然后，筛选 SPP1 作为靶基因，并使用蛋白质印迹分析在人心脏成纤维细胞 (HCF) 中进一步研究其促进纤维化的机制。

结果

检索后，本研究使用了 GSE14975、GSE31821、GSE79768、GSE115574 和 GSE128188 数据集。总共在左心房阑尾组织中鉴定出 147 个差异表达基因 (DEG)，在右心房阑尾组织中鉴定出 85 个差异表达基因。根据富集分析结果，发现钙信号通路在AF中起重要作用，其中EGFR、AGTR1、HTR2B、CD38和BDKRB1可能是关键基因。此外，SPP1 通过 PPI 分析被确定为关键驱动因素，并通过实验证明通过调节 PI3K/Akt 信号通路降低 p27 的表达，依次促进 HCF 纤维化。

结论

生物信息学分析表明，钙信号通路可能在 AF 中起重要作用，而 SPP1 可通过 PI3K/Akt/p27 信号轴促进心肌纤维化。