Comparative transcriptome profiling of three different murine modelsof metabolic dysfunction-associated steatohepatitis

Acta Universitatis Medicinalis Anhui 2025, 08, v.60 1445-1453     font:big middle small

Found programs: National Natural Science Foundation of China (No . 92268109)

Authors:Liu Tianwen',2 Guo Ziyi°’ , Bi Hanqi*, Zhou Bing', Lu Yan*, Mao Feis, Wang Hua'.2

Keywords:MASH ; murine models ; transcriptome ; comparative analysis ; differentially expressed genes ; meta⁃ bolic pathway

DOI:10.19405/j.cnki.issn1000-1492.2025.08.012

〔Abstract〕 To compare the transcriptomic profiles between three distinct metabolic dysfunction⁃associat⁃mal murine model that more closely resembles human MASH progression . Methods Forty 8 ⁃week⁃old male C57BL/6J mice were randomly assigned to either a control group fed normal chow diet ( NCD) or one of three MASH model groups receiving high⁃fat high⁃cholesterol diet (HFHCD) , choline⁃deficient high⁃fat diet (CDHFD) ,from three randomly selected mice per group were collected for mRNA sequencing ( mRNA⁃seq) analysis . Mean⁃bases . Overlap of functional profiles was analyzed by gene set enrichment analysis (GSEA) profiles to compare the mouse transcriptome with that of human patients at different stages of the disease . Additionally , Pearson ′s correla⁃tion analysis was used to explore the correlation between gene expression of murine models and human MASH . Re-sults Seven commonly up⁃regulated genes (Col1a1 , Smoc2 , Col6a1 , Gpx3 , Col16a1 , Spp1 and Crtap) were de⁃ways involving steatosis , hepatocellular injury and fibrosis were detected in the three MASH models at the pathway level . HFHCD and MCD might share more common traits . In comparing gene expression and pathway profiles be⁃tween different murine models and patients with different stages of MASH , all three murine MASH models showed a closer resemblance to the human progressive stages of MASH . Notably , the transcriptomic features of the CDHFD model were more consistent with those of human MASH . Conclusion There are certain similarities and differences among the transcriptional profiles of the three MASH models . The MASH models are more similar to the advanced stage of MASH in human patients . Compared to the other two models , the CDHFD model ′ s transcriptome profile more closely resembles human MASH .