Chronic Carbon Tetrachloride Applications Induced Hepatocyte Apoptosis in Lipocalin 2 Null Mice Through Endoplasmic Reticulum Stress and Unfolded Protein Response.

The lack of Lipocalin (LCN2) provokes overwhelming endoplasmic reticulum (ER) stress responses in vitro and in acute toxic liver injury models, resulting in hepatocyte apoptosis. LCN2 is an acute phase protein produced in hepatocytes in response to acute liver injuries. In line with these findings we investigated ER stress responses of mice in chronic ER stress using a long-term repetitive carbon tetrachloride (CCl) injection model.

Endoglin Trafficking/Exosomal Targeting in Liver Cells Depends on -Glycosylation.

Injury of the liver involves a wound healing partial reaction governed by hepatic stellate cells and portal fibroblasts. Individual members of the transforming growth factor-β (TGF-β) superfamily including TGF-β itself and bone morphogenetic proteins (BMP) exert diverse and partially opposing effects on pro-fibrogenic responses. Signaling by these ligands is mediated through binding to membrane integral receptors type I/type II.

Portal myofibroblasts are sensitive to CCN-mediated endoplasmic reticulum stress-related apoptosis with potential to attenuate biliary fibrogenesis.

Portal fibroblasts are mesenchyme-derived fibroblasts surrounding the bile ducts, and activated into portal myofibroblasts (pMF) during cholestatic liver injury. pMF express α-smooth muscle actin (α-SMA) and produce the fibrogenic extracellular matrix (ECM) collagen type I and fibronectin, playing important roles in portal fibrosis. A cholestatic bile duct-ligated (BDL) model is characterized by impaired hepatobiliary excretion of bile, leading to increased bile acid accumulation.

-Glycosylation of Lipocalin 2 Is Not Required for Secretion or Exosome Targeting.

Lipocalin 2 (LCN2) is a highly conserved secreted adipokine acting as a serum transport protein for small hydrophobic molecules such as fatty acids and steroids. In addition, LCN2 limits bacterial growth by sequestering iron-containing siderophores and further protects against intestinal inflammation and tumorigenesis associated with alterations in the microbiota. Human LCN2 contains one -glycosylation site conserved in other species.