title: Hepatic sinusoids in liver injury, inflammation, and fibrosis: new pathophysiological insights.
abstract: Changes of hepatic sinusoids are crucial in the pathogenesis of liver cirrhosis and portal hypertension. Liver injury leads to distinct morphological abnormalities such as loss of sinusoidal fenestration, vasoconstriction, and angiogenesis as well as molecular changes. Communication between the two key cells in this hepatic microenvironment-hepatic stellate cells (HSC) and sinusoidal endothelial cells (SEC)-has been studied for many years and several canonical pathways have been elucidated, such as decreased eNOS activity or increased PDGF and TGF-β production leading to activation and migration of HSC. In recent studies, alternative pathways of intercellular communication in liver diseases have been described such as cell-derived extracellular vesicles called exosomes, which deliver cell compounds to their target cells. Moreover, such extracellular vesicles may link injury to inflammation in alcoholic hepatitis. While inflammation leading to liver fibrosis has been studied in detail, in some circumstances pathways other than the known canonical inflammatory pathways may contribute to hepatic fibrogenesis. For example, in congestive hepatopathy, sinusoidal dilatation and fibrosis have been shown to be mediated by non-inflammatory mechanisms and associated with sinusoidal thrombi. A recently developed murine model further enables experimental studies of this disease entity. Increasing knowledge about these alternative disease pathways in liver injury, inflammation, and fibrosis may reveal possible target molecules for future therapies. This article builds upon a seminar given at the recent 3rd JSGE International Topic Conference in Sendai, Japan, and reviews the areas outlined above.
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Greuter
authors.affiliation: Gastroenterology Research Unit, Department of Gastroenterology and Hepatology, Mayo Clinic and Foundation, 200 First St. SW, Rochester, MN, 55905, USA. shah.vijay@mayo.edu.
authors.forename: Vijay H
authors.initials: VH
authors.lastname: Shah
mesh_terms: D002196:Capillaries / Q000503:physiopathology*; D002450:Cell Communication; D042783:Endothelial Cells / Q000502:physiology*; D055166:Hepatic Stellate Cells / Q000502:physiology*; D006801:Humans; D008107:Liver Diseases / Q000209:etiology*
keywords: Exosome signaling; Hepatic stellate cell; Intercellular communication; Intrasinusoidal thrombosis; Microvesicles; Sinusoidal epithelial cell