Silencing RGS7 attenuates atrial fibrillation progression by activating the cGMP-PKG signaling pathway

IF 4.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-03-13 DOI:10.1016/j.bbadis.2025.167786

Hao Huang , Yan Xiong , Jie Zeng

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Abstract

Background

Atrial fibrillation (AF) is a common diagnosed heart disease that needs novel managements. This study aimed to seek potential biomarkers and underlying regulatory pathways associated with AF.

Methods

Differential expressed genes (DEGs) were identified from the Gene Expression Omnibus database, followed by a protein-protein interaction (PPI) network to discover hub genes. Principal components analysis (PCA) and receiver operating characteristic (ROC) curves were performed to evaluate the ability of hub genes to discriminate between AF and control. RGS7 was selected as a key hub gene, and genes co-expressed with RGS7 were identified for functional enrichment analysis. Further in vivo and in vitro experiments were conducted to investigate the effects of silencing RGS7 on AF and the potential pathway.

Results

We identified top 5 hub genes (RGS7, EGFR, RGS4, GNA13 and RGS11) from the PPI network. PCA showed these genes could distinguish between AF and control samples, with 100 % of the area under curve (AUC) values. Silencing RGS7 inhibited cell apoptosis, inflammation and oxidative stress, and increased mitochondrial membrane potential in angiotensin II (AngII)-treated HL-1 cells, while overexpression of RGS7 reversed the inhibitory effects of silencing RGS7 on AF. Additionally, silencing RGS7 improved cardiac function and decreased cardiac fibrosis in AF rats. The cGMP-PKG signaling pathway was screened as a potential signal transduction pathway, and silencing RGS7 increased the expression of PKG1, while KT5823 blocked the process.

Conclusion

Silencing RGS7 attenuates AF by activating the cGMP-PKG signaling pathway, which may offer directions for selecting biomarkers and regulatory pathways for AF.

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通过激活 cGMP-PKG 信号通路，沉默 RGS7 可减轻心房颤动的进展。

背景：心房颤动（AF）是一种常见的心脏病，需要新的治疗方法。本研究旨在寻找与af相关的潜在生物标志物和潜在的调控途径。方法：从基因表达Omnibus数据库中鉴定差异表达基因（deg），然后通过蛋白-蛋白相互作用（PPI）网络发现枢纽基因。采用主成分分析（PCA）和受试者工作特征（ROC）曲线来评估中枢基因区分AF和对照组的能力。选择RGS7作为关键枢纽基因，鉴定与RGS7共表达的基因进行功能富集分析。进一步进行体内外实验，探讨沉默RGS7对房颤的影响及其可能的通路。结果：我们从PPI网络中鉴定出排名前5位的枢纽基因（RGS7、EGFR、RGS4、GNA13和RGS11）。主成分分析表明，这些基因可以区分AF和对照样品，其曲线下面积（AUC）值为100 %。沉默RGS7可抑制血管紧张素II （AngII）处理的HL-1细胞的细胞凋亡、炎症和氧化应激，并增加线粒体膜电位，而过表达RGS7逆转了沉默RGS7对房颤的抑制作用。此外，沉默RGS7可改善房颤大鼠的心功能，减少心脏纤维化。cGMP-PKG信号通路被筛选为潜在的信号转导通路，沉默RGS7可增加PKG1的表达，而KT5823可阻断该过程。结论：RGS7沉默通过激活cGMP-PKG信号通路减弱AF，这可能为AF生物标志物的选择和调控途径的选择提供指导。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biochimica et biophysica acta. Molecular basis of disease 生物-生化与分子生物学

CiteScore

12.30

自引率

0.00%

发文量

218

审稿时长

32 days

期刊介绍： BBA Molecular Basis of Disease addresses the biochemistry and molecular genetics of disease processes and models of human disease. This journal covers aspects of aging, cancer, metabolic-, neurological-, and immunological-based disease. Manuscripts focused on using animal models to elucidate biochemical and mechanistic insight in each of these conditions, are particularly encouraged. Manuscripts should emphasize the underlying mechanisms of disease pathways and provide novel contributions to the understanding and/or treatment of these disorders. Highly descriptive and method development submissions may be declined without full review. The submission of uninvited reviews to BBA - Molecular Basis of Disease is strongly discouraged, and any such uninvited review should be accompanied by a coverletter outlining the compelling reasons why the review should be considered.