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Journal Articles Scientific Reports Year : 2020

Hepatic stellate cell hypertrophy is associated with metabolic liver fibrosis

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Abstract

Hepatic fibrosis is a major consequence of chronic liver disease such as non-alcoholic steatohepatitis which is undergoing a dramatic evolution given the obesity progression worldwide, and has no treatment to date. Hepatic stellate cells (HSCs) play a key role in the fibrosis process, because in chronic liver damage, they transdifferentiate from a "quiescent" to an "activated" phenotype responsible for most the collagen deposition in liver tissue. Here, using a diet-induced liver fibrosis murine model (choline-deficient amino acid-defined, high fat diet), we characterized a specific population of HSCs organized as clusters presenting simultaneously hypertrophy of retinoid droplets, quiescent and activated HSC markers. We showed that hypertrophied HSCs co-localized with fibrosis areas in space and time. Importantly, we reported the existence of this phenotype and its association with collagen deposition in three other mouse fibrosis models, including CCl4-induced fibrosis model. Moreover, we have also shown its relevance in human liver fibrosis associated with different etiologies (obesity, non-alcoholic steatohepatitis, viral hepatitis C and alcoholism). In particular, we have demonstrated a significant positive correlation between the stage of liver fibrosis and HSC hypertrophy in a cohort of obese patients with hepatic fibrosis. These results lead us to conclude that hypertrophied HSCs are closely associated with hepatic fibrosis in a metabolic disease context and may represent a new marker of metabolic liver disease progression.
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Dates and versions

inserm-02506293 , version 1 (12-03-2020)

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Céline Hoffmann, Nour El Houda Djerir, Anne Danckaert, Julien Fernandes, Pascal Roux, et al.. Hepatic stellate cell hypertrophy is associated with metabolic liver fibrosis. Scientific Reports, 2020, 10 (1), pp.3850. ⟨10.1038/s41598-020-60615-0⟩. ⟨inserm-02506293⟩
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