Remodelin treatment reshapes inflammation-related transcriptomic signatures in experimental thalamic hemorrhage.

BACKGROUND

Thalamic hemorrhage is a severe subtype of intracerebral hemorrhage in which secondary neuroinflammation contributes to tissue injury and neurological deterioration. N-acetyltransferase 10 (NAT10), an RNA N4-acetylcytidine writer, has been implicated in inflammatory regulation and neurological disorders. However, inflammation-related transcriptomic changes associated with Remodelin treatment after thalamic hemorrhage remain unclear.

METHODS

mRNA transcriptome sequencing was performed on perilesional thalamic tissues from control, thalamic hemorrhage model, and Remodelin-treated mice. Differentially expressed genes were identified for the Model versus Control and Remodelin Intervention versus Model comparisons. Genes showing opposite directions of regulation across the two comparisons were defined as Remodelin-reversed differentially expressed genes. GeneCards-derived inflammation-related genes were converted to mouse orthologs and intersected with Remodelin-reversed genes. Protein-protein interaction analysis, Gene Ontology and KEGG enrichment analyses, gene set enrichment analysis, immune-cell signature estimation, and transcription factor/miRNA regulatory network prediction were performed. Key candidates were validated by quantitative RT-PCR.

RESULTS

RNA-seq identified 499 differentially expressed genes in the Model versus Control comparison and 664 in the Remodelin Intervention versus Model comparison. Among 46 shared differentially expressed genes, 42 showed opposite-direction regulation. Ortholog-corrected screening identified 9 Remodelin-reversed inflammation-related candidates: Cxcl1, Ccl2, Ncf4, Ptx3, Pomc, Masp2, Tnfrsf8, Card9, and Gpr84. Enrichment analyses linked these genes mainly to leukocyte- and neutrophil-mediated immunity, tumor necrosis factor production, cytokine-cytokine receptor interaction, IL-17 signaling, TNF signaling, chemokine signaling, and NOD-like receptor signaling. Protein-protein interaction analysis highlighted Ccl2, Cxcl1, and Pomc as prominent candidate nodes. qRT-PCR using independent biological samples provided preliminary transcript-level support for Remodelin-associated changes in Cxcl1 and Pomc expression, whereas Ccl2 was increased after hemorrhage but was not significantly reduced by Remodelin.

CONCLUSION

This study identifies Remodelin-reversed inflammation-related transcriptomic signatures in experimental thalamic hemorrhage. Cxcl1 and Pomc represent the most consistently supported Remodelin-responsive transcriptomic candidates, whereas Ccl2 appears to be a hemorrhage-associated inflammatory hub without robust reversal at the examined time point. These findings provide an exploratory neurogenomic framework for investigating inflammation-related transcriptional remodeling associated with Remodelin treatment.