Buniatian, Gayane Hrachia and Weiskirchen, Ralf and Weiss, Thomas S. and Schwinghammer, Ute and Fritz, Martin and Seferyan, Torgom and Proksch, Barbara and Glaser, Michael and Lourhmati, Ali and Buadze, Marine and Borkham-Kamphorst, Erawan and Gaunitz, Frank and Gleiter, Christoph H. and Lang, Thomas and Schaeffeler, Elke and Tremmel, Roman and Cynis, Holger and Frey, William H. and Gebhardt, Rolf and Friedman, Scott L. and Mikulits, Wolfgang and Schwab, Matthias and Danielyan, c (2020) Antifibrotic Effects of Amyloid-Beta and Its Loss in Cirrhotic Liver. CELLS, 9 (2): 452. ISSN , 2073-4409
Full text not available from this repository. (Request a copy)Abstract
The function and regulation of amyloid-beta (A beta) in healthy and diseased liver remains unexplored. Because A beta reduces the integrity of the blood-brain barrier we have examined its potential role in regulating the sinusoidal permeability of normal and cirrhotic liver. A beta 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 A beta more efficiently than astrocytes and HSC degraded A beta leading to suppressed expression of alpha-smooth muscle actin (alpha-SMA), collagen 1 and transforming growth factor beta (TGF beta). A beta also upregulated sinusoidal permeability marker endothelial NO synthase (eNOS) and decreased TGF beta in cultured human liver sinusoidal endothelial cells (hLSEC). Liver A beta 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 A beta in the maintenance of liver sinusoidal permeability and in protection against cirrhosis/fibrosis via attenuation of HSC activation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HEPATIC STELLATE CELLS; SINUSOIDAL ENDOTHELIAL-CELLS; FIBRILLARY ACIDIC PROTEIN; NITRIC-OXIDE SYNTHASE; SMOOTH-MUSCLE-CELLS; A-BETA; ALZHEIMERS-DISEASE; RAT-LIVER; OXIDATIVE STRESS; UP-REGULATION; liver cirrhosis; liver sinusoidal permeability; liver sinusoidal endothelial cells; hepatic stellate cells; beta secretase; presenilin; endothelial nitric oxide synthase; myelin basic protein; Alzheimer's disease; neprilysin; astrocytes |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Mar 2021 10:37 |
| Last Modified: | 30 Mar 2021 10:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/45174 |
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