Hepatitis B virus inhibits insulin receptor signaling and impairs liver regeneration via intracellular retention of the insulin receptor

摘要: Hepatitis B virus (HBV) causes severe liver disease but the underlying mechanisms are incompletely understood. During chronic HBV infection, is recurrently injured by immune cells in quest for viral elimination. To compensate tissue injury, regeneration represents a vital process which requires proliferative insulin receptor signaling. This study aims to investigate impact of on and hepatic After carbon tetrachloride-induced delayed transgenic mice. These mice show diminished hepatocyte proliferation increased expression fibrosis markers. accordance with reduced activation although induces via NF-E2-related factor 2. leads intracellular amounts expressing hepatocytes. However, retention simultaneously reduces amount functional receptors cell surface thereby attenuates binding vitro vivo. Intracellular caused elevated α-taxilin, free syntaxin protein, hepatocytes preventing proper targeting surface. Consequently, analyses responsiveness revealed that less sensitive stimulation leading regeneration. describes novel pathomechanism uncouples from signals impedes compensatory after injury.