Hepatic stellate cells as key target in liver fibrosis

By T. Higashi, S. Friedman, Yujin Hoshida. Advanced Drug Delivery Reviews, 2017

1,280 citations recorded by the source corpus.

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.

Subfields: Cell Biology, Epidemiology, Hepatology

View Paper: https://www.semanticscholar.org/paper/af86413d96a11f6a01049f9bd77ffad311c1dacb

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cell Biology

1. K. Guan
2. David M. Sabatini

In Epidemiology

1. K. Guan
2. M. Pinzani
3. Minyang Fu
4. M. Parola

In Hepatology

1. M. Pinzani
2. Minyang Fu
3. M. Parola

Citations in the corpus

• Pyroptosis in inflammatory diseases and cancer (2022, background): “The fibrosis-related proteins are mainly derived from hepatic stellate cells, which get activated and produce collagen through pyroptosis [80].”
• Liver fibrosis: Pathophysiology, pathogenetic targets and clinical issues. (2019, background): “Our present knowledge concerning phenotypic profibrogenic responses operated by hepatic MFs largely comes from studies on HSC and HSC/MFs performed either in vivo or in vitro by taking advantage of primary culture or immortalized cell lines of human or rodent HSC (Higashi et al., 2017) as well as of”
• The Hippo signalling pathway and its implications in human health and diseases (2022, background): “Hepatic stellate cells are important hepatic cells that can secrete various inflammatory molecules and extracellular matrix components to aid the progression of hepatic inflammation and fibrosis.(340,341) The effect of YAP/TAZ on the activation of hepatic stellate cells has been verified in multiple”