"Tipping" extracellular matrix remodeling towards regression of liver fibrosis: novel concepts

Fernando Magdaleno, Robert Schierwagen, Frank E Uschner, Jonel Trebicka

Publikation: Bidrag til tidsskriftReviewForskningpeer review

Resumé

Fibrosis development was initially conceived as an incessant progressive condition. Nowadays, it has become evident that fibrotic tissue undergoes a continuous two-way process: fibrogenesis and fibrinolysis, characterizing the remodeling of extracellular matrix (ECM). However, in established fibrosis, this two-way process is tipped towards fibrogenesis and this leads to a self-perpetuating accumulation of ECM, a distinct metabolic unit, together with other cells and processes promoting fibrosis deposition. Several mechanisms promote fibrosis regression, such as degradation of ECM, infiltration of restorative macrophages, prevention of the epithelial-mesenchymal transition of hepatocytes, restoration of the liver sinusoidal endothelial cells' differentiation phenotype, and reversion to quiescence, apoptosis and senescence of hepatic stellate cells (HSC). Hence, fibrosis is the result of an unbalanced two-way process of matrix remodeling. At the late stage of the disease, antifibrotic interventions could become necessary to reverse self-perpetuating fibrogenesis and accelerate regression of fibrosis even if cause and cofactors of hepatic injury have been eliminated. This review outlines some of the important mechanisms leading towards regression of liver fibrosis.

OriginalsprogEngelsk
TidsskriftMinerva Gastroenterologica e Dietologica
Vol/bind64
Udgave nummer1
Sider (fra-til)51-61
ISSN1121-421X
DOI
StatusUdgivet - 1. mar. 2018

Fingeraftryk

Liver Cirrhosis
Hepatic Stellate Cells
Liver
Fibrinolysis
Cell Differentiation
Hepatocytes
Macrophages
Apoptosis
Wounds and Injuries

Citer dette

Magdaleno, Fernando ; Schierwagen, Robert ; Uschner, Frank E ; Trebicka, Jonel. / "Tipping" extracellular matrix remodeling towards regression of liver fibrosis : novel concepts. I: Minerva Gastroenterologica e Dietologica. 2018 ; Bind 64, Nr. 1. s. 51-61.
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abstract = "Fibrosis development was initially conceived as an incessant progressive condition. Nowadays, it has become evident that fibrotic tissue undergoes a continuous two-way process: fibrogenesis and fibrinolysis, characterizing the remodeling of extracellular matrix (ECM). However, in established fibrosis, this two-way process is tipped towards fibrogenesis and this leads to a self-perpetuating accumulation of ECM, a distinct metabolic unit, together with other cells and processes promoting fibrosis deposition. Several mechanisms promote fibrosis regression, such as degradation of ECM, infiltration of restorative macrophages, prevention of the epithelial-mesenchymal transition of hepatocytes, restoration of the liver sinusoidal endothelial cells' differentiation phenotype, and reversion to quiescence, apoptosis and senescence of hepatic stellate cells (HSC). Hence, fibrosis is the result of an unbalanced two-way process of matrix remodeling. At the late stage of the disease, antifibrotic interventions could become necessary to reverse self-perpetuating fibrogenesis and accelerate regression of fibrosis even if cause and cofactors of hepatic injury have been eliminated. This review outlines some of the important mechanisms leading towards regression of liver fibrosis.",
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"Tipping" extracellular matrix remodeling towards regression of liver fibrosis : novel concepts. / Magdaleno, Fernando; Schierwagen, Robert; Uschner, Frank E; Trebicka, Jonel.

I: Minerva Gastroenterologica e Dietologica, Bind 64, Nr. 1, 01.03.2018, s. 51-61.

Publikation: Bidrag til tidsskriftReviewForskningpeer review

TY - JOUR

T1 - "Tipping" extracellular matrix remodeling towards regression of liver fibrosis

T2 - novel concepts

AU - Magdaleno, Fernando

AU - Schierwagen, Robert

AU - Uschner, Frank E

AU - Trebicka, Jonel

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Fibrosis development was initially conceived as an incessant progressive condition. Nowadays, it has become evident that fibrotic tissue undergoes a continuous two-way process: fibrogenesis and fibrinolysis, characterizing the remodeling of extracellular matrix (ECM). However, in established fibrosis, this two-way process is tipped towards fibrogenesis and this leads to a self-perpetuating accumulation of ECM, a distinct metabolic unit, together with other cells and processes promoting fibrosis deposition. Several mechanisms promote fibrosis regression, such as degradation of ECM, infiltration of restorative macrophages, prevention of the epithelial-mesenchymal transition of hepatocytes, restoration of the liver sinusoidal endothelial cells' differentiation phenotype, and reversion to quiescence, apoptosis and senescence of hepatic stellate cells (HSC). Hence, fibrosis is the result of an unbalanced two-way process of matrix remodeling. At the late stage of the disease, antifibrotic interventions could become necessary to reverse self-perpetuating fibrogenesis and accelerate regression of fibrosis even if cause and cofactors of hepatic injury have been eliminated. This review outlines some of the important mechanisms leading towards regression of liver fibrosis.

AB - Fibrosis development was initially conceived as an incessant progressive condition. Nowadays, it has become evident that fibrotic tissue undergoes a continuous two-way process: fibrogenesis and fibrinolysis, characterizing the remodeling of extracellular matrix (ECM). However, in established fibrosis, this two-way process is tipped towards fibrogenesis and this leads to a self-perpetuating accumulation of ECM, a distinct metabolic unit, together with other cells and processes promoting fibrosis deposition. Several mechanisms promote fibrosis regression, such as degradation of ECM, infiltration of restorative macrophages, prevention of the epithelial-mesenchymal transition of hepatocytes, restoration of the liver sinusoidal endothelial cells' differentiation phenotype, and reversion to quiescence, apoptosis and senescence of hepatic stellate cells (HSC). Hence, fibrosis is the result of an unbalanced two-way process of matrix remodeling. At the late stage of the disease, antifibrotic interventions could become necessary to reverse self-perpetuating fibrogenesis and accelerate regression of fibrosis even if cause and cofactors of hepatic injury have been eliminated. This review outlines some of the important mechanisms leading towards regression of liver fibrosis.

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KW - Remodeling

KW - Rho-associated kinases

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