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...
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doaj-1b69246c1cb74e4faf9f1de0fc1561e02020-11-25T02:10:50ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-06-012011270010.3390/ijms20112700ijms20112700ERK Pathway in Activated, Myofibroblast-Like, Hepatic Stellate Cells: A Critical Signaling Crossroad Sustaining Liver FibrosisBeatrice Foglia0Stefania Cannito1Claudia Bocca2Maurizio Parola3Erica Novo4Department Clinical and Biological Sciences, Unit of Experimental Medicine and Clinical Pathology, University of Torino, Corso Raffaello 30, 10125 Torino, ItalyDepartment Clinical and Biological Sciences, Unit of Experimental Medicine and Clinical Pathology, University of Torino, Corso Raffaello 30, 10125 Torino, ItalyDepartment Clinical and Biological Sciences, Unit of Experimental Medicine and Clinical Pathology, University of Torino, Corso Raffaello 30, 10125 Torino, ItalyDepartment Clinical and Biological Sciences, Unit of Experimental Medicine and Clinical Pathology, University of Torino, Corso Raffaello 30, 10125 Torino, ItalyDepartment Clinical and Biological Sciences, Unit of Experimental Medicine and Clinical Pathology, University of Torino, Corso Raffaello 30, 10125 Torino, ItalyFibrogenic 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.https://www.mdpi.com/1422-0067/20/11/2700ERK pathwayhepatic stellate cellsliver myofibroblastsliver fibrosischronic liver diseasesantifibrotic strategies |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Beatrice Foglia Stefania Cannito Claudia Bocca Maurizio Parola Erica Novo |
spellingShingle |
Beatrice Foglia Stefania Cannito Claudia Bocca Maurizio Parola Erica Novo ERK Pathway in Activated, Myofibroblast-Like, Hepatic Stellate Cells: A Critical Signaling Crossroad Sustaining Liver Fibrosis International Journal of Molecular Sciences ERK pathway hepatic stellate cells liver myofibroblasts liver fibrosis chronic liver diseases antifibrotic strategies |
author_facet |
Beatrice Foglia Stefania Cannito Claudia Bocca Maurizio Parola Erica Novo |
author_sort |
Beatrice Foglia |
title |
ERK Pathway in Activated, Myofibroblast-Like, Hepatic Stellate Cells: A Critical Signaling Crossroad Sustaining Liver Fibrosis |
title_short |
ERK Pathway in Activated, Myofibroblast-Like, Hepatic Stellate Cells: A Critical Signaling Crossroad Sustaining Liver Fibrosis |
title_full |
ERK Pathway in Activated, Myofibroblast-Like, Hepatic Stellate Cells: A Critical Signaling Crossroad Sustaining Liver Fibrosis |
title_fullStr |
ERK Pathway in Activated, Myofibroblast-Like, Hepatic Stellate Cells: A Critical Signaling Crossroad Sustaining Liver Fibrosis |
title_full_unstemmed |
ERK Pathway in Activated, Myofibroblast-Like, Hepatic Stellate Cells: A Critical Signaling Crossroad Sustaining Liver Fibrosis |
title_sort |
erk pathway in activated, myofibroblast-like, hepatic stellate cells: a critical signaling crossroad sustaining liver fibrosis |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-06-01 |
description |
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. |
topic |
ERK pathway hepatic stellate cells liver myofibroblasts liver fibrosis chronic liver diseases antifibrotic strategies |
url |
https://www.mdpi.com/1422-0067/20/11/2700 |
work_keys_str_mv |
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