Jeongjoo, Pyo Choi, Yong soo 2024-01-12T02:36:54Z 2024-01-12T02:36:54Z 2022-10-06 2022-10 https://pubs.kist.re.kr/handle/201004/76002 Background: Despite the global prevalence of nonalcoholic fatty liver disease (NAFLD), its pathophysiology remains unclear. In this study, we established highly confident nonalcoholic steatohepatitis (NASH) gene signatures and evaluated the pathological mechanisms underlying NASH through a systematic meta-analysis of transcriptome and proteome datasets obtained from NASH patients and mouse models. Methods: We analyzed NASH transcriptome datasets from 539 patients and 99 mice. A whole-liver tissue proteome dataset was used to confirm the protein level dysregulation of NASH signatures significant in both humans and mice. Results: In total, 254 human and 1,917 mouse NASH gene signatures were established. Up-regulated genes of 254 human signatures were associated with inflammation, steatosis, apoptosis, and extracellular matrix organization, whereas down-regulated genes were associated with response to metal ions and lipid and amino acid metabolism. When different mouse models were compared against humans, models with high fat and high fructose diet most closely resembled the genetic features of human NAFLD. Cross-species analysis revealed 66 genes that were concordantly dysregulated between human and mouse NASH. Among these, 14 genes were further validated to be dysregulated at the protein level. The resulting 14 genes included some of the well-established NASH associated genes and a promising NASH drug target. Functional enrichment analysis revealed that dysregulation of amino acid metabolism was the most significant hepatic perturbation in both human and mouse NASH. Conclusions: We established the most comprehensive hepatic gene signatures for NASH in humans and mice to date. To the best of our knowledge, this is the first study to collectively analyze the common signatures between human and mouse NASH on a transcriptome-proteome scale. English Frontiers Media S.A. Key hepatic signatures of human and mouse nonalcoholic steatohepatitis: A transcriptome-proteome data meta-analysis Article 10.3389/fendo.2022.934847 1 Frontiers in Endocrinology, v.13 Frontiers in Endocrinology 13 Y scie scopus 000871363400001 Endocrinology & Metabolism Endocrinology & Metabolism Review FATTY LIVER-DISEASE EXPRESSION PROFILES nonalcoholic fatty liver disease nonalcoholic steatohepatitis transcriptomics proteomics cross-species analysis