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. 2023 Nov 14;326(2):G147–G162. doi: 10.1152/ajpgi.00184.2023

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Published by the American Physiological Society.

Licensed under Creative Commons Attribution CC-BY 4.0. Published by the American Physiological Society.

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Figure 3. — Effect of cholestenoic acid (CA) on transcriptional activities in hepatocytes. HepG-2 cells were cultured in high glucose (HG) medium and treated with 20 µM of CA for 0, 3, 6, 12, and 24 h. A: number of downregulated genes regulated by CA. B: number of upregulated genes by CA. C: top Gene Ontology (GO) terms that are enriched by downregulated genes and treated by 20 µM CA for 6 h. CBP, cholesterol biosynthetic process; IBP, isoprenoid biosynthetic process; SBP, sterol biosynthetic process; SDBP, steroid biosynthetic process; IDBP, isopentenyl diphosphate biosynthetic process, mevalonate pathway; CI, cholesterol import; RN, response to nutrient; CMP, cholesterol metabolic process; CH, cholesterol homeostasis; NRLLPC, negative regulation of low-density lipoprotein particle clearance. D: top GO terms that were enriched by upregulated genes following treatment with 20 µM CA for 6 h. CRCI, cellular response to copper ion; CZIH, cellular zinc ion homeostasis; DCI, detoxification of copper ion; NRG, negative regulation of growth; CRZI, cellular response to zinc ion; CRCI, cellular response to cadmium ion; AMP, ATP metabolic process; CRE, cellular response to erythropoietin; ACO, actin cytoskeleton organization; PLAJ, protein localization to adherens junction. E: Kyoto Encyclopedia of Genes and Genome (KEGG) pathways enriched by downregulated genes treated by 20 µM CA for 6 h, involved gene numbers were labeled at the end of each bar. F: gene-gene network analysis revealed that the downregulated genes are involved in KEGG pathways. G: heatmap for the expression levels of downregulated genes that enriched in cholesterol metabolism, metabolic pathways, and steroid biosynthesis pathways. PCSK9, proprotein convertase subtilisin/kexin type 9; MVK, mevalonate kinase; HMGCS1, 3-hydroxy-3-methylglutaryl-CoA synthase 1; MVD, mevalonate diphosphate decarboxylase; MSMO1, methylsterol monooxygenase 1; IDI1, isopentenyl-diphosphate delta isomerase 1; HMGCR: 3-hydroxy-3-methylglutaryl-CoA reductase; FDFT1, farnesyl-diphosphate farnesyltransferase 1; CYP51A1, cytochrome P450 family 51 subfamily A member 1; HSD17B7, hydroxysteroid 17-β dehydrogenase 7.