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Cited by 78Liver physiology and pathologyLiver Disease Diagnosis and TreatmentLiver Diseases and Immunity

Hepatic stellate cell hypertrophy is associated with metabolic liver fibrosis

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Hoffmann, Céline, Djerir, Nour El Houda, Danckaert, Anne, Fernandes, Julien, Roux, Pascal, Charrueau, Christine, Lachagès, Anne-Marie, Charlotte, Frédéric +9 more·2020·Scientific Reports
DOI 10.1038/s41598-020-60615-0PMC PMC7052210
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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 CCl 4-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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  • Hepatic stellate cells, characterized by DES and VIM expressions, are central to liver fibrosis and extracellular matrix remodeling.

    “Hepatic stellate cells, characterized by DES and VIM expressions, are central to liver fibrosis and extracellular matrix remodeling34,36.”

    From ​Temporal proteomic profiling of iPSC-derived human liver organoids reveals optimal maturation for drug metabolism and toxicology (2026) · cites this paper as [36]

    The Introduction identifies hepatic stellate cells as major contributors to fibrosis and producers of extracellular matrix proteins. The Results section on HSC-specific markers identifies desmin (DES) as an HSC marker. Our copy does not establish VIM expression as a characteristic of these cells; a search for VIM returned no matching passage. (LLM, conf=0.86)

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Research works printed but not linked: 25

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Authors
Hoffmann, C., Djerir, N. E. H., Danckaert, A., Fernandes, J., Roux, P., Charrueau, C., Lachagès, A.-M., Charlotte, F., Brocheriou, I., Clément, K., Aron-Wisnewsky, J., Foufelle, F., Ratziu, V., Hainque, B., Bonnefont-Rousselot, D., Bigey, P., & Escriou, V.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Institut Pasteur (FR)
  • Assistance Publique – Hôpitaux de Paris (FR)
  • Inserm (FR)
Corresponding author
Hoffmann, Céline
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2020-03-02
Volume
10
Issue
1
Pages
3850-3850
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-020-60615-0
PMC
PMC7052210
OpenAlex
W3009847299
Cited by
78
References
3
Citations by year
2026: 11 · 2025: 10 · 2024: 18 · 2023: 14 · 2022: 12 · 2021: 11 · 2020: 2
FWCI
5.73
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
Funders
  • Agence Nationale de la Recherche (ANR-10-INSB-04-01)
  • Clinical Research Contract
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
Keywords
hepatic stellate cells, liver fibrosis, metabolic liver disease, nonalcoholic steatohepatitis, obesity, high-fat diet, collagen deposition, CCl4-induced fibrosis, hepatitis C, alcoholism, fibrosis biomarkers
MeSH terms
Animals, Carbon Tetrachloride Poisoning, Dietary Fats, Humans, Liver Cirrhosis, Male, Mice, Hepatic Stellate Cells

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