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Liver sinusoidal endothelial cells in hepatic fibrosis
Open accessAbstract
Capillarization, lack of liver sinusoidal endothelial cell (LSEC) fenestration, and formation of an organized basement membrane not only precedes fibrosis, but is also permissive for hepatic stellate cell activation and fibrosis. Thus, dysregulation of the LSEC phenotype is a critical step in the fibrotic process. Both a vascular endothelial growth factor (VEGF)‐stimulated, nitric oxide (NO)‐independent pathway and a VEGF‐stimulated NO‐dependent pathway are necessary to maintain the differentiated LSEC phenotype. The NO‐dependent pathway is impaired in capillarization and activation of this pathway downstream from NO restores LSEC differentiation in vivo . Restoration of LSEC differentiation in vivo promotes HSC quiescence, enhances regression of fibrosis, and prevents progression of cirrhosis. (H epatology 2015;61:1740–1746)
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“In healthy livers, LSECs prevent HSC activation [304].”
From Inflammation and immunity in liver homeostasis and disease: a nexus of hepatocytes, nonparenchymal cells and immune cells (2025) · cites this paper as [304]
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“Capillarized LSECs (Fig. 4), characterized by high nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-dependent collagen IV release [305], lose their HSC-suppressive properties and thereby contribute to an environment that favors HSC activation and fibrosis [304].”
From Inflammation and immunity in liver homeostasis and disease: a nexus of hepatocytes, nonparenchymal cells and immune cells (2025) · cites this paper as [304]
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Metadata
- Authors
- DeLeve, L. D.
- Affiliations
- University of Southern California (US)
- Corresponding author
- DeLeve, Laurie D.
- ORCID
- DeLeve, Laurie D.
- Venue
- Hepatology
- Published
- 2015-03-23
- Volume
- 61
- Issue
- 5
- Pages
- 1740-1746
- ISSN
- 0270-9139 (ISSN-L)
- 1527-3350
- PMC
- PMC4333127
- OpenAlex
- W1781806439
- Cited by
- 482
- References
- 50
- Citations by year
- 2026: 45 · 2025: 44 · 2024: 60 · 2023: 40 · 2022: 39 · 2021: 51 · 2020: 49 · 2019: 37 · 2018: 46 · 2017: 35 · 2016: 26 · 2015: 9
- FWCI
- 3.08
- Type
- journal article
- Language
- en
- Update notices
- correction (2015-07-01)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK100580, DK-66423, R01DK066423)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Keywords
- liver sinusoidal endothelial cells, liver fibrosis, capillarization, endothelial fenestrations, basement membrane formation, hepatic stellate cell activation, VEGF signaling, nitric oxide, HSC quiescence, fibrosis regression, liver cirrhosis
- MeSH terms
- Cell Differentiation, Humans, Liver Cirrhosis, Endothelial Cells
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