20.500.12556/RUL-134935 Common transcriptional program of liver fibrosis in mouse genetic models and humans Multifactorial metabolic diseases, such as non-alcoholic fatty liver disease, are a major burden to modern societies, and frequently present with no clearly defined molecular biomarkers. Herein we used system medicine approaches to decipher signatures of liver fibrosis in mouse models with malfunction in genes from unrelated biological pathways: cholesterol synthesis—Cyp51, notch signaling—Rbpj, nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) signaling—Ikbkg, and unknown lysosomal pathway—Glmp. Enrichment analyses of Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome and TRANScription FACtor (TRANSFAC) databases complemented with genome-scale metabolic modeling revealed fibrotic signatures highly similar to liver pathologies in humans. The diverse genetic models of liver fibrosis exposed a common transcriptional program with activated estrogen receptor alpha (ERα) signaling, and a network of interactions between regulators of lipid metabolism and transcription factors from cancer pathways and the immune system. The novel hallmarks of fibrosis are downregulated lipid pathways, including fatty acid, bile acid, and steroid hormone metabolism. Moreover, distinct metabolic subtypes of liver fibrosis were proposed, supported by unique enrichment of transcription factors based on the type of insult, disease stage, or potentially, also sex. The discovered novel features of multifactorial liver fibrotic pathologies could aid also in improved stratification of other fibrosis related pathologies. bile acid fatty acid fibrosis NAFLD NASH GEM žolčna kislina maščobna kislina fibroza true false true Angleški jezik Slovenski jezik Članek v reviji 2022-02-11 13:51:02 2022-02-11 13:51:10 2022-09-14 04:10:46 0000-00-00 00:00:00 2021 0 0 21 str. iss. 2, art. 832 Vol. 22 2021 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.3 1422-0067 10.3390/ijms22020832 47324419 RAZ_Blagotinsek_Cokan_Kaja_2021.pdf RAZ_Blagotinsek_Cokan_Kaja_2021.pdf 1 6E3BFBE3F2095EEFBA9B2A536C2A4066 9b1b09ff3e5dbbef3d50d6c4325e9bdb556f363c8aeb8cfa33fa4ab015c0ca4f 4e35aa9f-8b39-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=153696 https://www.mdpi.com/1422-0067/22/2/832 1 0eee43ce-8b39-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=153695 Medicinska fakulteta Fakulteta za računalništvo in informatiko 0 0 0