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Single-Cell RNA Sequencing Reveals RAC1 Involvement in Macrophages Efferocytosis in Diabetic Kidney Disease
Inflammation ( IF 5.1 ) Pub Date : 2023-12-08 , DOI: 10.1007/s10753-023-01942-y
Yi Song , Yifan Liu , Feng Guo , Lin Zhao , Guijun Qin

Macrophage-mediated inflammation plays a significant role in the development and progression of diabetic kidney disease (DKD). Studies have suggested that impaired macrophage efferocytosis aggravates the inflammatory response. However, its contribution to DKD progression remains unknown. Using single-cell RNA sequencing (scRNA-seq) data obtained from the GSE131882, GSE195460, GSE151302, GSE195460, and GSE131685 datasets, we successfully clustered 13 cell types. Through analysis of the ligand-receptor network, it was discovered that macrophages interact with other cells. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that macrophages exhibit a heightened presence of phagocytosis signaling. We discovered that RAC1 was closely related to macrophage efferocytosis through a Venn diagram and protein-protein interaction (PPI) analysis, which predicted the correlation with the clinical features of DKD using the NephroseqV5 tool. Furthermore, we verified that RAC1 exhibited decreased expression in macrophages cultured with lipopolysaccharide (LPS) and high glucose. Nevertheless, the overexpression of RAC1 promoted macrophage efferocytosis and inhibited the inflammatory response. In summary, our study focused on examining the presence and importance of efferocytosis-related molecules in DKD macrophages. Through a comprehensive analysis using scRNA-seq, we discovered that RAC1 plays a crucial role as an efferocytosis molecule in DKD. These findings enhance our current knowledge of the molecular mechanisms involved in the development of DKD and aid the exploration of new treatments.



中文翻译:

单细胞 RNA 测序揭示 RAC1 参与糖尿病肾病巨噬细胞胞吞作用

巨噬细胞介导的炎症在糖尿病肾病(DKD)的发生和进展中起着重要作用。研究表明,受损的巨噬细胞胞吞作用会加剧炎症反应。然而,其对 DKD 进展的贡献仍不清楚。使用从 GSE131882、GSE195460、GSE151302、GSE195460 和 GSE131685 数据集获得的单细胞 RNA 测序 (scRNA-seq) 数据,我们成功地对 13 种细胞类型进行了聚类。通过对配体-受体网络的分析,发现巨噬细胞与其他细胞相互作用。此外,基因本体论 (GO) 和京都基因和基因组百科全书 (KEGG) 富集分析表明,巨噬细胞表现出更强的吞噬信号传导。我们通过维恩图和蛋白质-蛋白质相互作用(PPI)分析发现RAC1与巨噬细胞胞吞作用密切相关,并使用NephroseqV5工具预测了与DKD临床特征的相关性。此外,我们验证了 RAC1 在用脂多糖 (LPS) 和高葡萄糖培养的巨噬细胞中表现出表达降低。然而,RAC1的过度表达促进了巨噬细胞的胞吞作用并抑制了炎症反应。总之,我们的研究重点是检查 DKD 巨噬细胞中胞吞作用相关分子的存在和重要性。通过使用scRNA-seq的综合分析,我们发现RAC1作为胞吞分子在DKD中发挥着至关重要的作用。这些发现增强了我们目前对 DKD 发展分子机制的了解,并有助于探索新的治疗方法。

更新日期:2023-12-08
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