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Adv Drug Deliv Rev. 2017 Nov 1;121:27-42. doi: 10.1016/j.addr.2017.05.007. Epub 2017 May 12.

Hepatic stellate cells as key target in liver fibrosis.

Author information

1
Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, USA; Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
2
Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, USA.
3
Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, USA. Electronic address: yujin.hoshida@mssm.edu.

Abstract

Progressive liver fibrosis, induced by chronic viral and metabolic disorders, leads to more than one million deaths annually via development of cirrhosis, although no antifibrotic therapy has been approved to date. Transdifferentiation (or "activation") of hepatic stellate cells is the major cellular source of matrix protein-secreting myofibroblasts, the major driver of liver fibrogenesis. Paracrine signals from injured epithelial cells, fibrotic tissue microenvironment, immune and systemic metabolic dysregulation, enteric dysbiosis, and hepatitis viral products can directly or indirectly induce stellate cell activation. Dysregulated intracellular signaling, epigenetic changes, and cellular stress response represent candidate targets to deactivate stellate cells by inducing reversion to inactivated state, cellular senescence, apoptosis, and/or clearance by immune cells. Cell type- and target-specific pharmacological intervention to therapeutically induce the deactivation will enable more effective and less toxic precision antifibrotic therapies.

KEYWORDS:

Alcoholic liver disease; Cirrhosis; Hepatitis; Myofibroblast; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis

PMID:
28506744
PMCID:
PMC5682243
DOI:
10.1016/j.addr.2017.05.007
[Indexed for MEDLINE]
Free PMC Article

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