Reversibility of Liver Fibrosis and Inactivation of Fibrogenic Myofibroblasts
TLDR
Understanding the mechanism of inactivation of hepatic stellate cells on cessation of fibrogenic stimuli may identify new approaches to cause already existing activated liver fibrosis cells/myofibroblasts to revert to a quiescent-like state.Abstract:
Many studies have demonstrated that hepatic fibrosis is reversible. Regression of liver fibrosis is associated with resorption of fibrous scar and the disappearance of collagen-producing myofibroblasts. The fate of these myofibroblasts has been recently revealed: some myofibroblasts undergo senescence and apoptosis during reversal of fibrosis, whereas other myofibroblasts revert to a quiescent-like phenotype. Inactivation of myofibroblasts is a newly described phenomenon (Kisseleva et al. in Proc. Natl .Acad. Sci. USA 109:9448–9453, 2012) which now requires mechanistic investigation. Understanding the mechanism of inactivation of hepatic stellate cells on cessation of fibrogenic stimuli may identify new approaches to cause already existing activated hepatic stellate cells/myofibroblasts to revert to a quiescent-like state. This review summarizes the research on the inactivation of hepatic myofibroblasts.read more
Citations
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2016 Comprehensive Update of the Banff Working Group on Liver Allograft Pathology: Introduction of Antibody-Mediated Rejection.
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Senescence of activated stellate cells limits liver fibrosis
Valery Krizhanovsky,Monica Yon,Monica Yon,Ross A. Dickins,Stephen Hearn,Janelle Simon,Janelle Simon,Cornelius Miething,Herman T. Yee,Lars Zender,Scott W. Lowe,Scott W. Lowe +11 more
TL;DR: In this paper, the authors show that senescent cells accumulate in murine livers treated to produce fibrosis, a precursor pathology to cirrhosis, derived primarily from activated hepatic stellate cells, which initially proliferate in response to liver damage and produce the extracellular matrix.
Journal ArticleDOI
Homozygous disruption of the murine MDR2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease
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Journal Article
Senescence of Activated Stellate Cells Limits Liver Fibrosis
Valery Krizhanovsky,Monica Yon,Monica Yon,Ross A. Dickins,Stephen Hearn,Janelle Simon,Janelle Simon,Cornelius Miething,Herman T. Yee,Lars Zender,Scott W. Lowe,Scott W. Lowe +11 more
TL;DR: It is shown that senescent cells accumulate in murine livers treated to produce fibrosis, a precursor pathology to cirrhosis, and natural killer cells preferentially kill senescent activated stellate cells in vitro and in vivo, thereby facilitating the resolution of fibrosis.
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