The Power of Plasticity—Metabolic Regulation of Hepatic Stellate Cells
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Hepatic stellate cells (HSCs) are resident non-parenchymal liver pericytes whose plasticity enables them to regulate a remarkable range of physiologic and pathologic responses. To support their functions in health and disease, HSCs engage pathways regulating carbohydrate, mitochondrial, lipid, and retinoid homeostasis. In chronic liver injury, HSCs drive hepatic fibrosis and are implicated in inflammation and cancer. To do so, the cells activate, or transdifferentiate, from a quiescent state into proliferative, motile myofibroblasts that secrete extracellular matrix, which demands rapid adaptation to meet a heightened energy need. Adaptations include reprogramming of central carbon metabolism, enhanced mitochondrial number and activity, endoplasmic reticulum stress, and liberation of free fatty acids through autophagy-dependent hydrolysis of retinyl esters that are stored in cytoplasmic droplets. As an archetype for pericytes in other tissues, recognition of the HSC's metabolic drivers and vulnerabilities offer the potential to target these pathways therapeutically to enhance parenchymal growth and modulate repair.
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Activation of HSCs in culture is associated with increased glycolysis, lipolysis, and glutaminolysis, which provide energy for this energy-intensive process.
“In particular, the activation of HSCs in culture is associated with increased glycolysis, lipolysis, and glutaminolysis, which provide the energy needed for this energy-intensive process (as detailed in (182)).”
From Found in translation—Fibrosis in metabolic dysfunction–associated steatohepatitis (MASH) (2023) · cites this paper as [182]
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Self-citationImpaired Hepatic Vitamin A Metabolism in NAFLD Mice Leading to Vitamin A Accumulation in Hepatocytes
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The anti Fibrotic effect of Aramchol on liver Fibrosis in TAA animal model
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- Authors
- Trivedi, P., Wang, S., & Friedman, S. L.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Friedman, Scott L.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2021-02
- Volume
- 33
- Issue
- 2
- Pages
- 242-257
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC7858232
- OpenAlex
- W3110189951
- Cited by
- 427
- References
- 195
- Citations by year
- 2026: 86 · 2025: 105 · 2024: 81 · 2023: 78 · 2022: 50 · 2021: 27
- FWCI
- 5.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK56621)
- American Gastroenterological Association (AGA2020-13-03)
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- hepatic stellate cells, cellular plasticity, metabolic regulation, liver fibrosis, chronic liver injury, myofibroblast transdifferentiation, central carbon metabolism, mitochondrial metabolism, endoplasmic reticulum stress, autophagy, free fatty acids, extracellular matrix secretion, liver inflammation, liver cancer, pericytes
- MeSH terms
- Cell Plasticity, Animals, Humans, Hepatic Stellate Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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