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

Gayane Hrachia Buniatian; Ralf Weiskirchen; Thomas S. Weiss; Ute Schwinghammer; Martin Fritz; Torgom Seferyan; Barbara Proksch; Michael Glaser; Ali Lourhmati; Marine Buadze; Erawan Borkham-Kamphorst; Frank Gaunitz; Christoph H. Gleiter; Thomas Lang; Elke Schaeffeler; Roman Tremmel; Holger Cynis; William H. Frey; Rolf Gebhardt; Scott L. Friedman; Wolfgang Mikulits; Matthias Schwab; Lusine Danielyan

doi:10.3390/cells9020452

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

Gayane Hrachia Buniatian, Ralf Weiskirchen, Thomas S. Weiss, Ute Schwinghammer, Martin Fritz, Torgom Seferyan, Barbara Proksch, Michael Glaser, Ali Lourhmati, Marine Buadze, Erawan Borkham-Kamphorst, Frank Gaunitz, Christoph H. Gleiter, Thomas Lang, Elke Schaeffeler, Roman Tremmel, Holger Cynis, William H. Frey, Rolf Gebhardt, Scott L. FriedmanWolfgang Mikulits, Matthias Schwab, Lusine Danielyan

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

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.

Original language	English
Article number	2638
Journal	Cells
Volume	9
Issue number	2
DOIs	https://doi.org/10.3390/cells9020452
State	Published - 17 Feb 2020

Keywords

Alzheimer’s disease
astrocytes
beta secretase
endothelial nitric oxide synthase
hepatic stellate cells
liver cirrhosis
liver sinusoidal endothelial cells
liver sinusoidal permeability
myelin basic protein
neprilysin
presenilin

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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., Gebhardt, R., ... Danielyan, L. (2020). Antifibrotic Effects of Amyloid-Beta and Its Loss in Cirrhotic Liver. Cells, 9(2), Article 2638. https://doi.org/10.3390/cells9020452

@article{12fbdad09baf4631ae251b2a9a8935fa,

title = "Antifibrotic Effects of Amyloid-Beta and Its Loss in Cirrhotic Liver",

abstract = "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.",

keywords = "Alzheimer{\textquoteright}s disease, astrocytes, beta secretase, endothelial nitric oxide synthase, hepatic stellate cells, liver cirrhosis, liver sinusoidal endothelial cells, liver sinusoidal permeability, myelin basic protein, neprilysin, presenilin",

author = "Buniatian, {Gayane Hrachia} and Ralf Weiskirchen and Weiss, {Thomas S.} and Ute Schwinghammer and Martin Fritz and Torgom Seferyan and Barbara Proksch and Michael Glaser and Ali Lourhmati and Marine Buadze and Erawan Borkham-Kamphorst and Frank Gaunitz and Gleiter, {Christoph H.} and Thomas Lang and Elke Schaeffeler and Roman Tremmel and Holger Cynis and Frey, {William H.} and Rolf Gebhardt and Friedman, {Scott L.} and Wolfgang Mikulits and Matthias Schwab and Lusine Danielyan",

year = "2020",

month = feb,

day = "17",

doi = "10.3390/cells9020452",

language = "English",

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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, Gebhardt, R, Friedman, SL, Mikulits, W, Schwab, M & Danielyan, L 2020, 'Antifibrotic Effects of Amyloid-Beta and Its Loss in Cirrhotic Liver', Cells, vol. 9, no. 2, 2638. https://doi.org/10.3390/cells9020452

TY - JOUR

T1 - Antifibrotic Effects of Amyloid-Beta and Its Loss in Cirrhotic Liver

AU - Buniatian, Gayane Hrachia

AU - Weiskirchen, Ralf

AU - Weiss, Thomas S.

AU - Schwinghammer, Ute

AU - Fritz, Martin

AU - Seferyan, Torgom

AU - Proksch, Barbara

AU - Glaser, Michael

AU - Lourhmati, Ali

AU - Buadze, Marine

AU - Borkham-Kamphorst, Erawan

AU - Gaunitz, Frank

AU - Gleiter, Christoph H.

AU - Lang, Thomas

AU - Schaeffeler, Elke

AU - Tremmel, Roman

AU - Cynis, Holger

AU - Frey, William H.

AU - Gebhardt, Rolf

AU - Friedman, Scott L.

AU - Mikulits, Wolfgang

AU - Schwab, Matthias

AU - Danielyan, Lusine

PY - 2020/2/17

Y1 - 2020/2/17

N2 - 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.

AB - 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.

KW - Alzheimer’s disease

KW - astrocytes

KW - beta secretase

KW - endothelial nitric oxide synthase

KW - hepatic stellate cells

KW - liver cirrhosis

KW - liver sinusoidal endothelial cells

KW - liver sinusoidal permeability

KW - myelin basic protein

KW - neprilysin

KW - presenilin

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U2 - 10.3390/cells9020452

DO - 10.3390/cells9020452

M3 - Article

C2 - 32089540

AN - SCOPUS:85098096423

SN - 2073-4409

VL - 9

JO - Cells

JF - Cells

IS - 2

M1 - 2638

ER -

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

Abstract

Keywords

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