Endoglin in human liver disease and murine models of liver fibrosis—A protective factor against liver fibrosis

Abstract

Background & Aims: Liver fibrosis is the outcome of chronic liver injury. Transforming growth factor-β (TGF-β) is a major profibrogenic cytokine modulating hepatic stellate cell (HSC) activation and extracellular matrix homeostasis. This study analyses the effect of Endoglin (Eng), a TGF-β type III auxiliary receptor, on fibrogenesis in two models of liver injury by HSC-specific endoglin deletion. Methods: Eng expression was measured in human and murine samples of liver injury. After generating GFAPCre(+)EngΔHSC mice, the impact of Endoglin deletion on chronic liver fibrosis was analysed. For in vitro analysis, Engflox/flox HSCs were infected with Cre-expressing virus to deplete Endoglin and fibrogenic responses were analysed. Results: Endoglin is upregulated in human liver injury. The receptor is expressed in liver tissues and mesenchymal liver cells with much higher abundance of the L-Eng splice variant. Comparing GFAPCre(−)Engf/f to GFAPCre(+)EngΔHSC mice in toxic liver injury, livers of GFAPCre(+)EngΔHSC mice showed 39.9% (P