Bulk RNA sequencing reveals endothelial STING-dependent transcriptional programs in murine metabolic dysfunction-associated steatohepatitis

Here, we investigate how endothelial-intrinsic cGAS-STING signaling integrates metabolic stress signals to reshape the hepatic niche in metabolic dysfunction-associated steatohepatitis (MASH). We performed bulk RNA sequencing on liver tissues from endothelial cell-specific Sting knockout mice (Stingfl/fl Cdh5-Cre+) and littermate controls (Stingfl/fl Cdh5-Cre-) subjected to a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) for 10 weeks.

Gene set enrichment analysis revealed that multiple cancer-associated and fibrogenic signaling pathways were enriched in control livers but markedly suppressed in StingΔEC livers. Conversely, pathways related to T cell regulation and metabolism were preferentially enriched in StingΔEC livers, indicating that endothelial-intrinsic STING signaling drives MASH progression by reshaping T cell-mediated immune responses.