Proteomic profiling of murine biliary-derived hepatic organoids and their capacity for drug disposition, bio-activation and detoxification
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ABSTRACT: Hepatic organoids are a recent innovation in in vitro modelling. Initial studies suggest organoids better recapitulate the liver phenotype in vitro compared to pre-existing proliferative cell models. However, their propensity for drug metabolism and detoxification remains poorly characterised. A global proteomic profiling of undifferentiated and differentiated hepatic murine organoids and donor-matched livers was therefore performed to assess both their similarity to liver tissue and DMET expression. iTRAQ analysis revealed 4,405 proteins commonly detected across all sample types. Differentiation of organoids significantly increased the expression of multiple CYP450s, phase II enzymes, liver biomarkers and hepatic transporters. While the final phenotype of differentiated organoids is distinct from liver tissue, they contain multiple DMET proteins necessary for liver function and drug metabolism, such as CYP450 3A, GSTA and MDR1A. Hepatic organoids may therefore represent an attractive novel model for hepatotoxicity testing, although further experimentation, optimisation and characterisation is needed relative to pre-existing models to fully contextualise their use as a putative in vitro model of DILI.
INSTRUMENT(S): TripleTOF 6600
ORGANISM(S): Mus Musculus (mouse)
TISSUE(S): Liver
SUBMITTER: Rosalind Jenkins
LAB HEAD: Rosalind Elspeth Jenkins
PROVIDER: PXD017986 | Pride | 2021-06-03
REPOSITORIES: Pride
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