Hepatic stellate cells as key target in liver fibrosis

Takaaki Higashi, Scott L. Friedman, Yujin Hoshida

Research output: Contribution to journalReview article

129 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)27-42
Number of pages16
JournalAdvanced Drug Delivery Reviews
Volume121
DOIs
StatePublished - Nov 1 2017
Externally publishedYes

Fingerprint

Hepatic Stellate Cells
Liver Cirrhosis
Dysbiosis
Myofibroblasts
Cell Aging
Poisons
Epigenomics
Hepatitis
Fibrosis
Epithelial Cells
Pharmacology
Apoptosis
Liver
Therapeutics
Proteins

Keywords

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

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Hepatic stellate cells as key target in liver fibrosis. / Higashi, Takaaki; Friedman, Scott L.; Hoshida, Yujin.

In: Advanced Drug Delivery Reviews, Vol. 121, 01.11.2017, p. 27-42.

Research output: Contribution to journalReview article

Higashi, Takaaki ; Friedman, Scott L. ; Hoshida, Yujin. / Hepatic stellate cells as key target in liver fibrosis. In: Advanced Drug Delivery Reviews. 2017 ; Vol. 121. pp. 27-42.
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