Hepatic stellate cells as key target in liver fibrosis

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


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.

Publication types

  • Review
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Hepatic Stellate Cells / drug effects*
  • Hepatic Stellate Cells / metabolism
  • Hepatic Stellate Cells / pathology
  • Humans
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / pathology*
  • Myofibroblasts / drug effects
  • Myofibroblasts / metabolism
  • Myofibroblasts / pathology