Hepatocyte Thorns, A Novel Drug-Induced Stress Response in Human and Mouse Liver Spheroids.

ABSTRACT: The in vivo-relevant phenotype of 3D liver spheroids allows for long-term studies of, e.g., novel mechanisms of chronic drug-induced liver toxicity. Using this system, we present a novel drug-induced stress response in human and murine hepatocyte spheroids, wherein long slender filaments form after chronic treatment with four different drugs, of which three are PPARα antagonists. The morphology of the thorns varies between donors and the compounds used. They are mainly composed of diverse protein fibres, which are glycosylated. Their formation is inhibited by treatment with fatty acids or antioxidants. Treatment of mice with GW6471 revealed changes in gene and protein expression, such as those in the spheroids. In addition, similar changes in keratin expression were seen following the trea

SUBMITTER: Pridgeon CS 

PROVIDER: S-EPMC9139950 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature