Importance of Endocytic Pathways in Liver Function and Disease

Abstract

Hepatocellular endocytosis is a highly dynamic process responsible for the internalization of a variety of different receptor ligand complexes, trophic factors, lipids, and, unfortunately, many different pathogens. The uptake of these external agents has profound effects on seminal cellular processes including signaling cascades, migration, growth, and proliferation. The hepatocyte, like other well-polarized epithelial cells, posses a host of different endocytic mechanisms and entry routes to ensure the selective internalization of cargo molecules. These pathways include receptor-mediated endocytosis, lipid raft associated endocytosis, caveolae, or fluid-phase uptake although there are likely many others. Understanding and defining the regulatory mechanisms underlying these distinct entry routes, sorting and vesicle formation, as well as the postendocytic trafficking pathways is of high importance especially in the liver, as their mis-regulation can contribute to aberrant liver pathology and liver diseases. Further, these processes can be “hijacked” by a variety of different infectious agents and viruses. This review provides an overview of common components of the endocytic and postendocytic trafficking pathways utilized by hepatocytes. It will also discuss in more detail how these general themes apply to liver-specific processes including iron homeostasis, HBV infection, and even hepatic steatosis.

Identification of Diagnostic Biomarkers and Subtypes of Liver Hepatocellular Carcinoma by Multi-Omics Data Analysis

“…With the help of the spliceosome, endocytosis acted as one of main activators for finding a series of successive waves of maternal pioneer signal regulators [61]. The misregulation of endocytosis could result in HCC [62].…”

Inhibitory effect of silibinin on hepatitis B virus entry

“…CME plays important roles in hepatocytes, which uptake various materials physiologically [17] , and it is thought that hepatitis viruses utilize this system. A previous report showed that silibinin attenuated HCV infection via the inhibition of CME, and this study showed it also inhibits HBV infection.…”

Hepatitis B Virus Entry into Cells

“…Several other lines of evidence support the notion that CME is the major route of entry for HBV in vivo ( Figure 2 ). Indeed, CME has been shown to play a number of important roles in hepatocytes, in iron homeostasis, hepatic steatosis, and virus-induced liver infections [ 83 ]. In addition to acting as the receptor for HBV, NTCP has a physiological function in the uptake of bile salts and is recycled to the plasma membrane via CME [ 84 ].…”