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

"Tipping" extracellular matrix remodelling towards regression of liver fibrosis: novel concepts. Minerva Gastroenterol Dietol. 2017 Sep 11;: Authors: Magdaleno F, Schierwagen R, Uschner FE, Trebicka J 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, as well as 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 and highligh...
Source: Minerva Gastroenterologica e Dietologica - Category: Gastroenterology Tags: Minerva Gastroenterol Dietol Source Type: research