Hepatic Stellate Cell Activation and Inactivation in NASH-Fibrosis-Roles as Putative Treatment Targets?

Hepatic fibrosis is the primary predictor of mortality in patients with non-alcoholic steatohepatitis (NASH). In this process, the activated hepatic stellate cells (HSCs) constitute the principal cells responsible for the deposition of a fibrous extracellular matrix, thereby driving the hepatic scar...

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Bibliographic Details
Published in:Biomedicines 2021-03, Vol.9 (4), p.365
Main Authors: Zisser, Alexandra, Ipsen, David H, Tveden-Nyborg, Pernille
Format: Article
Language:English
Subjects:
Cell activation
Cellular stress response
Chemokines
Cytokines
Drug development
Extracellular matrix
Fibrosis
Gene expression
Genotype & phenotype
Growth factors
hepatic stellate cells
HSC activation
HSC inactivation
Inflammation
Ligands
Lipids
Liver
Metabolism
Metabolites
Mortality
non-alcoholic fatty liver disease
non-alcoholic steatohepatitis
Review
Signal transduction
Stellate cells
Therapeutic targets
Tumor necrosis factor-TNF
Veins & arteries
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Summary:Hepatic fibrosis is the primary predictor of mortality in patients with non-alcoholic steatohepatitis (NASH). In this process, the activated hepatic stellate cells (HSCs) constitute the principal cells responsible for the deposition of a fibrous extracellular matrix, thereby driving the hepatic scarring. HSC activation, migration, and proliferation are controlled by a complex signaling network involving growth factors, lipotoxicity, inflammation, and cellular stress. Conversely, the clearance of activated HSCs is a prerequisite for the resolution of the extracellular fibrosis. Hence, pathways regulating the fate of the HSCs may represent attractive therapeutic targets for the treatment and prevention of NASH-associated hepatic fibrosis. However, the development of anti-fibrotic drugs for NASH patients has not yet resulted in clinically approved therapeutics, underscoring the complex biology and challenges involved when targeting the intricate cellular signaling mechanisms. This narrative review investigated the mechanisms of activation and inactivation of HSCs with a focus on NASH-associated hepatic fibrosis. Presenting an updated overview, this review highlights key cellular pathways with potential value for the development of future treatment modalities.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines9040365