Relevance of FXR-p62/SQSTM1 pathway for survival and protection of mouse hepatocytes and liver, especially with steatosis

摘要: Liver injury and regeneration involve complicated processes are affected by various physio-pathological conditions. Surgically, severe liver after surgical resection often leads to fatal failure, especially with some underlying pathological conditions such as steatosis. Therefore, protection from the of hepatocytes is a serious concern in clinical settings. We studied effects farnesoid X receptor (FXR) on cell survival steatosis mouse (AML12 cells) investigated their molecular mechanisms. next whether or not FXR improves injury, model partial hepatectomy (PH) An FXR-specific agonist, GW4064, induced expressions p62/SQSTM1 gene protein AML12 cells. Because we previously reported key molecule for antioxidation hepatocytes, examined activation nuclear factor erythroid 2-related factor-2 (Nrf2) induction antioxidant molecules GW4064. GW4064 activated Nrf2 subsequently (Nrf2, catalase, HO-1, thioredoxin). also pro-survival protective associated p62/SQSTM1. Expectedly, phosphorylation Akt, expression anti-apoptotic (Bcl-xL Bcl-2), reduced harmful hepatic (Fas ligand Fas). promoted hepatocyte survival, which was cancelled siRNA. These findings suggest potential relevance FXR-p62/SQSTM1 pathway hepatocytes. Furthermore, small heterodimer partners (SHP) suppressed (LXR)-induced expecting vivo effect In db/db mice fatty liver, pre-treatment significantly post-PH (serum levels LDH, AST & ALT histological study) improved The molecules, p62/SQSTM1, SHP were upregulated tissue treatment. present study first demonstrate -SHP against