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Single-Cell RNA Sequencing Reveals RAC1 Involvement in Macrophages Efferocytosis in Diabetic Kidney Disease

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Abstract

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.

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DATA AVAILABILITY

Data are available from authors upon reasonable request.

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Funding

This work was supported by grants from the National Natural Science Foundation of China (81974110, 82170839) to Qin, from the National Natural Science Foundation of China (82300930) to Song, and Hubei Chen Xiaoping Science and Technology Development Foundation (CXPJJH122012-023) to Song.

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  1. Yi Song and Yifan Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Yi Song, Feng Guo, Lin Zhao & Guijun Qin

  2. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

    Yifan Liu

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Contributions

YS and YL: conceptualization, methodology, software, investigation, formal analysis, writing – original draft. FG: resources, supervision, data curation, writing – original draft. LZ: visualization, investigation, validation. GQ: conceptualization, funding acquisition, resources, supervision, writing – review and editing.

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Correspondence to Guijun Qin.

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Song, Y., Liu, Y., Guo, F. et al. Single-Cell RNA Sequencing Reveals RAC1 Involvement in Macrophages Efferocytosis in Diabetic Kidney Disease. Inflammation 47, 753–770 (2024). https://doi.org/10.1007/s10753-023-01942-y

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