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Article

Modelling Nonalcoholic Steatohepatitis In Vivo—A Close Transcriptomic Similarity Supports the Guinea Pig Disease Model

1
Section of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1870 Frederikberg, Denmark
2
Center for non-coding RNA in Technology and Health, Department of Veterinary and Animal Sciences, Section for Animal Genetics, Bioinformatics and Breeding, University of Copenhagen, DK-1871 Frederiksberg, Denmark
3
Liver Disease Research, Global Drug Discovery, Novo Nordisk A/S, DK-2760 Måløv, Denmark
*
Author to whom correspondence should be addressed.
Shared first-authorship.
Academic Editors: François R. Jornayvaz and Karim Gariani
Biomedicines 2021, 9(9), 1198; https://doi.org/10.3390/biomedicines9091198
Received: 15 August 2021 / Revised: 7 September 2021 / Accepted: 9 September 2021 / Published: 10 September 2021
(This article belongs to the Special Issue NAFLD: From Mechanisms to Therapeutic Approaches)
The successful development of effective treatments against nonalcoholic steatohepatitis (NASH) is significantly set back by the limited availability of predictive preclinical models, thereby delaying and reducing patient recovery. Uniquely, the guinea pig NASH model develops hepatic histopathology and fibrosis resembling that of human patients, supported by similarities in selected cellular pathways. The high-throughput sequencing of guinea pig livers with fibrotic NASH (n = 6) and matched controls (n = 6) showed a clear separation of the transcriptomic profile between NASH and control animals. A comparison to NASH patients with mild disease (GSE126848) revealed a 45.2% overlap in differentially expressed genes, while pathway analysis showed a 34% match between the top 50 enriched pathways in patients with advanced NASH (GSE49541) and guinea pigs. Gene set enrichment analysis highlighted the similarity to human patients (GSE49541), also when compared to three murine models (GSE52748, GSE38141, GSE67680), and leading edge genes THRSP, CCL20 and CD44 were highly expressed in both guinea pigs and NASH patients. Nine candidate genes were identified as highly correlated with hepatic fibrosis (correlation coefficient > 0.8), and showed a similar expression pattern in NASH patients. Of these, two candidate genes (VWF and SERPINB9) encode secreted factors, warranting further investigations as potential biomarkers of human NASH progression. This study demonstrates key similarities in guinea pig and human NASH, supporting increased predictability when translating research findings to human patients. View Full-Text
Keywords: nonalcoholic steatohepatitis; fibrosis; transcriptome; animal model; guinea pig; biomarkers nonalcoholic steatohepatitis; fibrosis; transcriptome; animal model; guinea pig; biomarkers
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MDPI and ACS Style

Skat-Rørdam, J.; Ipsen, D.H.; Seemann, S.E.; Latta, M.; Lykkesfeldt, J.; Tveden-Nyborg, P. Modelling Nonalcoholic Steatohepatitis In Vivo—A Close Transcriptomic Similarity Supports the Guinea Pig Disease Model. Biomedicines 2021, 9, 1198. https://doi.org/10.3390/biomedicines9091198

AMA Style

Skat-Rørdam J, Ipsen DH, Seemann SE, Latta M, Lykkesfeldt J, Tveden-Nyborg P. Modelling Nonalcoholic Steatohepatitis In Vivo—A Close Transcriptomic Similarity Supports the Guinea Pig Disease Model. Biomedicines. 2021; 9(9):1198. https://doi.org/10.3390/biomedicines9091198

Chicago/Turabian Style

Skat-Rørdam, Josephine, David H. Ipsen, Stefan E. Seemann, Markus Latta, Jens Lykkesfeldt, and Pernille Tveden-Nyborg. 2021. "Modelling Nonalcoholic Steatohepatitis In Vivo—A Close Transcriptomic Similarity Supports the Guinea Pig Disease Model" Biomedicines 9, no. 9: 1198. https://doi.org/10.3390/biomedicines9091198

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