Journal of inflammation research
Shared Tissue-Level Molecular Signatures and Immunometabolic Associations in Nonalcoholic Steatohepatitis and Chronic Kidney Disease: Potential Endothelial Relevance
By Qiao R, Zhang J, Gao Y and 1 others.
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.