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2020
Journal Article
Titel
Antifibrotic effects of amyloid-beta and its loss in cirrhotic liver
Abstract
The function and regulation of amyloid-beta (Av) in healthy and diseased liver remains unexplored. Because Av reduces the integrity of the blood-brain barrier we have examined its potential role in regulating the sinusoidal permeability of normal and cirrhotic liver. Av and key proteins that generate (beta-secretase 1 and presenilin-1) and degrade it (neprilysin and myelin basic protein) were decreased in human cirrhotic liver. In culture, activated hepatic stellate cells (HSC) internalized Av more efficiently than astrocytes and HSC degraded Av leading to suppressed expression of a-smooth muscle actin (a-SMA), collagen 1 and transforming growth factor v (TGFv). Av also upregulated sinusoidal permeability marker endothelial NO synthase (eNOS) and decreased TGFv in cultured human liver sinusoidal endothelial cells (hLSEC). Liver Av levels also correlate with the expression of eNOS in transgenic Alzheimer's disease mice and in human and rodent cirrhosis/fibrosis. These findings suggest a previously unexplored role of Av in the maintenance of liver sinusoidal permeability and in protection against cirrhosis/fibrosis via attenuation of HSC activation.
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