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Open AccessArticle

Antifibrotic Effects of Amyloid-Beta and Its Loss in Cirrhotic Liver

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Department of Clinical Pharmacology, University Hospital of Tübingen, 72076 Tübingen, Germany
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H. Buniatian Institute of Biochemistry, National Academy of Sciences of the Republic of Armenia (NAS RA), Yerevan 0014, Armenia
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Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, RWTH University Hospital Aachen, 52074 Aachen, Germany
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Children’s University Hospital (KUNO), University of Regensburg, 93053 Regensburg, Germany
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Department of Neurosurgery, University Hospital of Leipzig, 04103 Leipzig, Germany
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Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, Germany, and University of Tuebingen, 72076 Tuebingen, Germany
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Department of Drug Design and Target Validation, Fraunhofer Institute for Cell Therapy and Immunology, 06120 Halle, Germany
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Center for Memory & Aging, HealthPartners Neuroscience Center, St. Paul, MN 55130, USA
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Rudolf-Schönheimer Institute of Biochemistry, Faculty of Medicine, University of Leipzig, 04103 Leipzig, Germany
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Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029-6574, USA
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Department of Medicine I, Institute of Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Vienna 1090, Austria
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Department of Pharmacy and Biochemistry, University of Tuebingen, 72076 Tuebingen, Germany
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Departments of Biochemistry and Clinical Pharmacology, and Neuroscience Laboratory, Yerevan State Medical University, Yerevan 0025, Armenia
*
Authors to whom correspondence should be addressed.
Cells 2020, 9(2), 452; https://doi.org/10.3390/cells9020452
Received: 23 December 2019 / Revised: 6 February 2020 / Accepted: 13 February 2020 / Published: 17 February 2020
The function and regulation of amyloid-beta (Aβ) in healthy and diseased liver remains unexplored. Because Aβ reduces the integrity of the blood-brain barrier we have examined its potential role in regulating the sinusoidal permeability of normal and cirrhotic liver. Aβ 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 Aβ more efficiently than astrocytes and HSC degraded Aβ leading to suppressed expression of α-smooth muscle actin (α-SMA), collagen 1 and transforming growth factor β (TGFβ). Aβ also upregulated sinusoidal permeability marker endothelial NO synthase (eNOS) and decreased TGFβ in cultured human liver sinusoidal endothelial cells (hLSEC). Liver Aβ 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 Aβ in the maintenance of liver sinusoidal permeability and in protection against cirrhosis/fibrosis via attenuation of HSC activation. View Full-Text
Keywords: 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 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
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MDPI and ACS Style

Buniatian, G.H.; Weiskirchen, R.; Weiss, T.S.; Schwinghammer, U.; Fritz, M.; Seferyan, T.; Proksch, B.; Glaser, M.; Lourhmati, A.; Buadze, M.; Borkham-Kamphorst, E.; Gaunitz, F.; Gleiter, C.H.; Lang, T.; Schaeffeler, E.; Tremmel, R.; Cynis, H.; Frey, W.H., II; Gebhardt, R.; Friedman, S.L.; Mikulits, W.; Schwab, M.; Danielyan, L. Antifibrotic Effects of Amyloid-Beta and Its Loss in Cirrhotic Liver. Cells 2020, 9, 452. https://doi.org/10.3390/cells9020452

AMA Style

Buniatian GH, Weiskirchen R, Weiss TS, Schwinghammer U, Fritz M, Seferyan T, Proksch B, Glaser M, Lourhmati A, Buadze M, Borkham-Kamphorst E, Gaunitz F, Gleiter CH, Lang T, Schaeffeler E, Tremmel R, Cynis H, Frey WH II, Gebhardt R, Friedman SL, Mikulits W, Schwab M, Danielyan L. Antifibrotic Effects of Amyloid-Beta and Its Loss in Cirrhotic Liver. Cells. 2020; 9(2):452. https://doi.org/10.3390/cells9020452

Chicago/Turabian Style

Buniatian, Gayane H.; Weiskirchen, Ralf; Weiss, Thomas S.; Schwinghammer, Ute; Fritz, Martin; Seferyan, Torgom; Proksch, Barbara; Glaser, Michael; Lourhmati, Ali; Buadze, Marine; Borkham-Kamphorst, Erawan; Gaunitz, Frank; Gleiter, Christoph H.; Lang, Thomas; Schaeffeler, Elke; Tremmel, Roman; Cynis, Holger; Frey, William H., II; Gebhardt, Rolf; Friedman, Scott L.; Mikulits, Wolfgang; Schwab, Matthias; Danielyan, Lusine. 2020. "Antifibrotic Effects of Amyloid-Beta and Its Loss in Cirrhotic Liver" Cells 9, no. 2: 452. https://doi.org/10.3390/cells9020452

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