α2-Adrenergic Receptor in Liver Fibrosis: Implications for the Adrenoblocker Mesedin

Schwinghammer, Ute A.; Melkonyan, Magda M.; Hunanyan, Lilit; Tremmel, Roman; Weiskirchen, Ralf; Borkham-Kamphorst, Erawan; Schaeffeler, Elke; Seferyan, Torgom; Mikulits, Wolfgang; Yenkoyan, Konstantin; Schwab, Matthias; Danielyan, Lusine

doi:10.3390/cells9020456

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α2-Adrenergic Receptor in Liver Fibrosis: Implications for the Adrenoblocker Mesedin

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Erawan Borkham-Kamphorst

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^1,3,7,8 and

^1,*

Department of Clinical Pharmacology, University Hospital of Tuebingen, 72076 Tuebingen, Germany

Department of Medical Chemistry, Yerevan State Medical University, 0025 Yerevan, Armenia

Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, 70376 Stuttgart, Germany, and University of Tuebingen, 72074 Tuebingen, Germany

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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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H. Buniatian Institute of Biochemistry, National Academy of Sciences of the Republic of Armenia (NAS RA), 0014 Yerevan, Armenia

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Department of Medicine I, Institute of Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria

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Department of Biochemistry and Neuroscience Laboratory, Yerevan State Medical University, 0025 Yerevan, Armenia

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Department of Biochemistry and Pharmacy, University of Tuebingen, 72076 Tuebingen, Germany

Author to whom correspondence should be addressed.

Cells 2020, 9(2), 456; https://doi.org/10.3390/cells9020456

Received: 2 January 2020 / Revised: 6 February 2020 / Accepted: 13 February 2020 / Published: 18 February 2020

(This article belongs to the Special Issue Cellular and Molecular Mechanisms Underlying the Pathogenesis of Hepatic Fibrosis)

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Abstract

The noradrenergic system is proposed to play a prominent role in the pathogenesis of liver fibrosis. While α1- and β-adrenergic receptors (ARs) are suggested to be involved in a multitude of profibrogenic actions, little is known about α2-AR-mediated effects and their expression pattern during liver fibrosis and cirrhosis. We explored the expression of α2-AR in two models of experimental liver fibrosis. We further evaluated the capacity of the α2-AR blocker mesedin to deactivate hepatic stellate cells (HSCs) and to increase the permeability of human liver sinusoidal endothelial cells (hLSECs). The mRNA of α2a-, α2b-, and α2c-AR subtypes was uniformly upregulated in carbon tetrachloride-treated mice vs the controls, while in bile duct-ligated mice, only α2b-AR increased in response to liver injury. In murine HSCs, mesedin led to a decrease in α-smooth muscle actin, transforming growth factor-β and α2a-AR expression, which was indicated by RT-qPCR, immunocytochemistry, and Western blot analyses. In a hLSEC line, an increased expression of endothelial nitric oxide synthase was detected along with downregulated transforming growth factor-β. In conclusion, we suggest that the α2-AR blockade alleviates the activation of HSCs and may increase the permeability of liver sinusoids during liver injury. View Full-Text

Keywords: α2-adrenoceptors; norepinephrine; mesedin; hepatic stellate cells; sinusoidal endothelial cells; liver fibrosis; sinusoidal permeability

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MDPI and ACS Style

Schwinghammer, U.A.; Melkonyan, M.M.; Hunanyan, L.; Tremmel, R.; Weiskirchen, R.; Borkham-Kamphorst, E.; Schaeffeler, E.; Seferyan, T.; Mikulits, W.; Yenkoyan, K.; Schwab, M.; Danielyan, L. α2-Adrenergic Receptor in Liver Fibrosis: Implications for the Adrenoblocker Mesedin. Cells 2020, 9, 456. https://doi.org/10.3390/cells9020456

AMA Style

Schwinghammer UA, Melkonyan MM, Hunanyan L, Tremmel R, Weiskirchen R, Borkham-Kamphorst E, Schaeffeler E, Seferyan T, Mikulits W, Yenkoyan K, Schwab M, Danielyan L. α2-Adrenergic Receptor in Liver Fibrosis: Implications for the Adrenoblocker Mesedin. Cells. 2020; 9(2):456. https://doi.org/10.3390/cells9020456

Chicago/Turabian Style

Schwinghammer, Ute A., Magda M. Melkonyan, Lilit Hunanyan, Roman Tremmel, Ralf Weiskirchen, Erawan Borkham-Kamphorst, Elke Schaeffeler, Torgom Seferyan, Wolfgang Mikulits, Konstantin Yenkoyan, Matthias Schwab, and Lusine Danielyan. 2020. "α2-Adrenergic Receptor in Liver Fibrosis: Implications for the Adrenoblocker Mesedin" Cells 9, no. 2: 456. https://doi.org/10.3390/cells9020456

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α2-Adrenergic Receptor in Liver Fibrosis: Implications for the Adrenoblocker Mesedin

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