Work

Shared Tissue-Level Molecular Signatures and Immunometabolic Associations in Nonalcoholic Steatohepatitis and Chronic Kidney Disease: Potential Endothelial Relevance

Year: 2026

Type: article

Abstract: Purpose: NASH and CKD are closely associated epidemiologically and share metabolic, inflammatory, and fibrotic features. This study integrated bulk-tissue transcriptomic datasets from both diseases to investigate shared tissue-level molecular signatures and their potential endothelial and immunometabolic relevance. Methods: Transcriptomic datasets from the Gene Expression Omnibus (GEO) for NASH and CKD were integrated to screen for common differentially expressed genes (co-DEGs). A protein-protein interaction network was constructed to identify ten hub genes. Single-sample Gene Set Enrichment Analysis (ssGSEA) and single-gene GSEA were performed to elucidate functional pathways. In vitro, human umbilical vein endothelial cells (HUVECs) were stimulated with palmitic acid (PA) and indoxyl sulfate (IS) to model NASH and CKD, respectively. Quantitative real-time PCR (qPCR), Western blotting, tube formation assays, and migration assays were employed to validate the expression of hub genes and functional phenotypic changes in endothelial cells. Results: A total of 156 commonly differentially expressed genes were identified. Protein-protein interaction network analysis revealed 10 hub genes, all of which showed a downregulated expression pattern. Immune infiltration analysis indicated that CCL2 and ICAM1 were positively correlated with the abundance of MDSCs and Th1 cells, respectively. Single-gene GSEA further showed that downregulation of these hub genes was closely associated with suppressed mitochondrial energy metabolism, mitophagy, and antioxidant defense pathways. qPCR and Western blotting confirmed downregulation in cell models, and treatment with PA/IS significantly impaired HUVEC tube formation and migration. Conclusion: This study identified a shared tissue-level molecular signature with potential endothelial relevance across NASH and CKD. The findings suggest that endothelial alterations may participate in an interconnected metabolic-redox-immune-fibrotic network. Because bulk-tissue data cannot determine cellular origin, the observed downregulation may also reflect changes in cellular states or tissue composition. However, the cellular origin and underlying causal mechanisms remain to be established.

Source: Journal of Inflammation Research

DOI: 10.2147/jir.s623639

Authors: Rui Qiao, Jian Zhang, Yinghui Gao, Xin Li

Institutions: Peking University, Beijing Ditan Hospital, Capital Medical University

Language: English

Topic: Liver Disease Diagnosis and Treatment

Subfield: Hepatology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,836