Integrated Transcriptomic and Single-Cell Analysis Reveals Shared Macrophage-Associated Inflammatory Signatures in MASLD/NAFLD and Rheumatoid Arthritis
- 1College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China
Abstract
Metabolic dysfunction-associated steatotic liver disease/nonalcoholic fatty liver disease (MASLD/NAFLD) and rheumatoid arthritis (RA) may share inflammatory mechanisms, although their common cellular basis remains unclear. We integrated bulk transcriptomic datasets (GSE66676 and GSE55235), single-cell RNA-sequencing datasets from murine RA synovium (GSE192504) and NASH liver (GSE129516), disease-association analysis, molecular docking, and in vitro experiments in LPS-stimulated RAW264.7 macrophages. Bulk transcriptomic analysis identified 630 shared differentially expressed genes, including 344 concordantly upregulated genes enriched in immune response, cytokine and chemokine signaling, phagosome, Toll-like receptor signaling, and Fc receptor-mediated phagocytosis; a strict dual-dataset intersection further defined 18 core genes significantly upregulated in both diseases. Immune-signature analysis indicated altered myeloid cell-associated inflammatory activity in both diseases, and several shared genes, including S100A8, S100A9, FCER1G, FCGR3A, LYZ, and MS4A7, correlated positively with monocyte/macrophage-related signatures. Single-cell analysis identified macrophage subsets with high S100a9 expression and elevated shared myeloid inflammatory signature scores in both RA synovium and NASH liver. Triptolide showed favorable predicted binding to the S100A8/A9 complex and reduced LPS-induced inflammatory cytokine secretion and expression of the six-gene signature in RAW264.7 cells, supporting the hypothesis that S100A9-associated inflammatory macrophage activation represents a candidate target for further investigation. These findings support a shared S100A9-positive inflammatory macrophage-associated program in MASLD/NAFLD and RA, and support the hypothesis that the S100A8/A9 complex represents a candidate target for further investigation.
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BibTeX
@article{yu2026integrated,
title = {{Integrated Transcriptomic and Single-Cell Analysis Reveals Shared Macrophage-Associated Inflammatory Signatures in MASLD/NAFLD and Rheumatoid Arthritis}},
author = {Wenbo Yu and Qianqian Nie and Yanze Wu and Xintian Lan and Jing Liu and Duoduo Xu and Shuguang Guan},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209150},
url = {https://www.mdpi.com/1422-0067/27/20/9150},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Integrated Transcriptomic and Single-Cell Analysis Reveals Shared Macrophage-Associated Inflammatory Signatures in MASLD/NAFLD and Rheumatoid Arthritis
AU - Wenbo Yu
AU - Qianqian Nie
AU - Yanze Wu
AU - Xintian Lan
AU - Jing Liu
AU - Duoduo Xu
AU - Shuguang Guan
PY - 2026
DA - 2026/10/15
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209150
UR - https://www.mdpi.com/1422-0067/27/20/9150
AB - Metabolic dysfunction-associated steatotic liver disease/nonalcoholic fatty liver disease (MASLD/NAFLD) and rheumatoid arthritis (RA) may share inflammatory mechanisms, although their common cellular basis remains unclear. We integrated bulk transcriptomic datasets (GSE66676 and GSE55235), single-cell RNA-sequencing datasets from murine RA synovium (GSE192504) and NASH liver (GSE129516), disease-association analysis, molecular docking, and in vitro experiments in LPS-stimulated RAW264.7 macrophages. Bulk transcriptomic analysis identified 630 shared differentially expressed genes, including 344 concordantly upregulated genes enriched in immune response, cytokine and chemokine signaling, phagosome, Toll-like receptor signaling, and Fc receptor-mediated phagocytosis; a strict dual-dataset intersection further defined 18 core genes significantly upregulated in both diseases. Immune-signature analysis indicated altered myeloid cell-associated inflammatory activity in both diseases, and several shared genes, including S100A8, S100A9, FCER1G, FCGR3A, LYZ, and MS4A7, correlated positively with monocyte/macrophage-related signatures. Single-cell analysis identified macrophage subsets with high S100a9 expression and elevated shared myeloid inflammatory signature scores in both RA synovium and NASH liver. Triptolide showed favorable predicted binding to the S100A8/A9 complex and reduced LPS-induced inflammatory cytokine secretion and expression of the six-gene signature in RAW264.7 cells, supporting the hypothesis that S100A9-associated inflammatory macrophage activation represents a candidate target for further investigation. These findings support a shared S100A9-positive inflammatory macrophage-associated program in MASLD/NAFLD and RA, and support the hypothesis that the S100A8/A9 complex represents a candidate target for further investigation.
SN - 1422-0067
ER -