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

Ute A. Schwinghammer, Magda M. Melkonyan, Lilit Hunanyan, Roman Tremmel, Ralf Weiskirchen, Erawan Borkham-Kamphorst, Elke Schaeffeler, Torgom Seferyan, Wolfgang Mikulits, Konstantin Yenkoyan, Matthias Schwab, Lusine Danielyan
2020 Cells  
The noradrenergic system is proposed to play a prominent role in the pathogenesis of liver fibrosis. While α1and 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
more » ... e 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.
doi:10.18154/rwth-conv-242155 fatcat:n5ovh7jinza3xpfjw6rn2mikri