ERK Pathway in Activated, Myofibroblast-Like, Hepatic Stellate Cells: A Critical Signaling Crossroad Sustaining Liver Fibrosis

Fibrogenic progression of chronic liver disease, whatever the etiology, is characterized by persistent chronic parenchymal injury, chronic activation of inflammatory response, and sustained activation of liver fibrogenesis, and of pathological wound healing response. A critical role in liver fibroge...

Full description

Saved in:
Bibliographic Details
Published in:International journal of molecular sciences 2019-06, Vol.20 (11), p.2700
Main Authors: Foglia, Beatrice, Cannito, Stefania, Bocca, Claudia, Parola, Maurizio, Novo, Erica
Format: Article
Language:English
Subjects:
Actin
Activation
Angiogenesis
antifibrotic strategies
Apoptosis
Chemokines
chronic liver diseases
Cytokines
ERK pathway
Etiology
Extracellular signal-regulated kinase
Fibrosis
Growth factors
hepatic stellate cells
Hepatitis
Inflammation
Inflammatory response
Kinases
Liver
Liver cirrhosis
Liver diseases
liver fibrosis
liver myofibroblasts
Metabolic pathways
Muscles
Peptides
Phosphorylation
Raf protein
Review
Signal transduction
Smooth muscle
Stellate cells
Wound healing
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Fibrogenic progression of chronic liver disease, whatever the etiology, is characterized by persistent chronic parenchymal injury, chronic activation of inflammatory response, and sustained activation of liver fibrogenesis, and of pathological wound healing response. A critical role in liver fibrogenesis is played by hepatic myofibroblasts (MFs), a heterogeneous population of α smooth-muscle actin-positive cells that originate from various precursor cells through a process of activation and transdifferentiation. In this review, we focus the attention on the role of extracellular signal-regulated kinase (ERK) signaling pathway as a critical one in modulating selected profibrogenic phenotypic responses operated by liver MFs. We will also analyze major therapeutic antifibrotic strategies developed in the last two decades in preclinical studies, some translated to clinical conditions, designed to interfere directly or indirectly with the Ras/Raf/MEK/ERK signaling pathway in activated hepatic MFs, but that also significantly increased our knowledge on the biology and pathobiology of these fascinating profibrogenic cells.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms20112700