Low-density lipoprotein receptors in liver: old acquaintances and a newcomer

The lipoprotein receptors low-density lipoprotein receptor (LDLR), the low-density lipoprotein receptor-related protein 1 (LRP1) and megalin/LRP2 share characteristic structural elements. In addition to their well-known roles in endocytosis of lipoproteins and systemic lipid homeostasis, it has been established that LRP1 mediates the endocytotic clearance of a multitude of extracellular ligands and regulates diverse signaling processes such as growth factor signaling, inflammatory signaling pathways, apoptosis, and phagocytosis in liver. Here, possible functions of LRP1 expression in hepatocytes and non-parenchymal cells in healthy and injured liver are discussed. Recent studies indicate the expression of megalin (LRP2) by hepatic stellate cells, myofibroblasts and Kupffer cells and hypothesize that LRP2 might represent another potential regulator of hepatic inflammatory processes. These observations provide the experimental framework for the systematic and dynamic analysis of the LDLR family during chronic liver injury and fibrogenesis.