Transcriptomic signatures of progressive and regressive liver fibrosis and portal hypertension

Petrenko, Oleksandr; Königshofer, Philipp; Brusilovskaya, Ksenia; Hofer, Benedikt S.; Bareiner, Katharina; Simbrunner, Benedikt; Jühling, Frank; Baumert, Thomas F.; Lupberger, Joachim; Trauner, Michael; Kauschke, Stefan G.; Pfisterer, Larissa; Simon, Eric; Rendeiro, André F.; de Rooij, Laura P.M.H.; Schwabl, Philipp; Reiberger, Thomas

doi:10.1016/j.isci.2024.109301

Cited by 1 publication

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References 75 publications

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“…The SPP1 and THRSP genes have also been shown to be among the top 10 differentially expressed genes, in line with our previous research using thioacetamide liver injection in guinea pigs and rats [ 11 ]. In fact, SPP1 is an important biomarker for fibrosis [ 22 ]. FGF21 is another significant gene, and according to recent research, it plays a significant role in lipid metabolism and reduces hepatocyte damage [ 23 , 24 , 25 , 26 , 27 ].…”

Section: Resultsmentioning

confidence: 99%

Probing Liver Injuries Induced by Thioacetamide in Human In Vitro Pooled Hepatocyte Experiments

Goel,

Printz,

Pannala

et al. 2024

IJMS

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Animal studies are typically utilized to understand the complex mechanisms associated with toxicant-induced hepatotoxicity. Among the alternative approaches to animal studies, in vitro pooled human hepatocytes have the potential to capture population variability. Here, we examined the effect of the hepatotoxicant thioacetamide on pooled human hepatocytes, divided into five lots, obtained from forty diverse donors. For 24 h, pooled human hepatocytes were exposed to vehicle, 1.33 mM (low dose), and 12 mM (high dose) thioacetamide, followed by RNA-seq analysis. We assessed gene expression variability using heat maps, correlation plots, and statistical variance. We used KEGG pathways and co-expression modules to identify underlying physiological processes/pathways. The co-expression module analysis showed that the majority of the lots exhibited activation for the bile duct proliferation module. Despite lot-to-lot variability, we identified a set of common differentially expressed genes across the lots with similarities in their response to amino acid, lipid, and carbohydrate metabolism. We also examined efflux transporters and found larger lot-to-lot variability in their expression patterns, indicating a potential for alteration in toxicant bioavailability within the cells, which could in turn affect the gene expression patterns between the lots. Overall, our analysis highlights the challenges in using pooled hepatocytes to understand mechanisms of toxicity.

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