Tight Junction Proteins and the Biology of Hepatobiliary Disease

Abstract

Tight junctions (TJ) are intercellular adhesion complexes on epithelial cells and composed of integral membrane proteins as well as cytosolic adaptor proteins. Tight junction proteins have been recognized to play a key role in health and disease. In the liver, TJ proteins have several functions: they contribute as gatekeepers for paracellular diffusion between adherent hepatocytes or cholangiocytes to shape the blood-biliary barrier (BBIB) and maintain tissue homeostasis. At non-junctional localizations, TJ proteins are involved in key regulatory cell functions such as differentiation, proliferation, and migration by recruiting signaling proteins in response to extracellular stimuli. Moreover, TJ proteins are hepatocyte entry factors for the hepatitis C virus (HCV)—a major cause of liver disease and cancer worldwide. Perturbation of TJ protein expression has been reported in chronic HCV infection, cholestatic liver diseases as well as hepatobiliary carcinoma. Here we review the physiological function of TJ proteins in the liver and their implications in hepatobiliary diseases.

Ultrastructural Features of Gold Nanoparticles Interaction with HepG2 and HEK293 Cells in Monolayer and Spheroids

“…Morphology of HepG2 cells was shown to keep main features of the hepatocytes: tight junctions separate apical and basolateral plasmalemma providing formation of bile capillaries and blood-biliary barrier; ultrastructural observations were supported by immunohistochemical and biochemical studies [ 38 , 39 ]. Based on current knowledge about the role of tight junctions in hepatic physiology and pathology, it is possible to claim that formation of these structures by HepG2 cells evidences for high levels of differentiation [ 40 ].…”

Zonula occludens and nasal epithelial barrier integrity in allergic rhinitis

“…The TJ barrier controls the diffusion of molecules by acting as semipermeable diffusion barriers through the paracellular pathway. It has been reported that transmembrane proteins such as claudin and occludin are essential for the regulation of paracellular permeability (Balda & Matter, 2000;Lee, 2015;Roehlen et al, 2020). ZO-1 is also responsible for the regulation of paracellular permeability (i.e., permeability for the passage of molecules between adjacent epithelial cells) via TJ complexes as it binds directly to transmembrane proteins (Balda & Matter, 2000;Lee, 2015;Roehlen et al, 2020).…”

“…It has been reported that transmembrane proteins such as claudin and occludin are essential for the regulation of paracellular permeability (Balda & Matter, 2000;Lee, 2015;Roehlen et al, 2020). ZO-1 is also responsible for the regulation of paracellular permeability (i.e., permeability for the passage of molecules between adjacent epithelial cells) via TJ complexes as it binds directly to transmembrane proteins (Balda & Matter, 2000;Lee, 2015;Roehlen et al, 2020). Loss of ZO-1 can retard the formation of the TJ complexes, and further breakdown of ZO-1 may result in severe disruption of the paracellular barrier in epithelial cells (Roehlen et al, 2020).…”

“…ZO-1 is also responsible for the regulation of paracellular permeability (i.e., permeability for the passage of molecules between adjacent epithelial cells) via TJ complexes as it binds directly to transmembrane proteins (Balda & Matter, 2000;Lee, 2015;Roehlen et al, 2020). Loss of ZO-1 can retard the formation of the TJ complexes, and further breakdown of ZO-1 may result in severe disruption of the paracellular barrier in epithelial cells (Roehlen et al, 2020). Hence, ZO-1 plays important roles in maintaining the epithelial barrier by connecting TJ molecules to seal the epithelial cells from infiltration of environmental allergens.…”

Peer Review #1 of "Zonula occludens and nasal epithelial barrier integrity in allergic rhinitis (v0.1)"

“…The TJ barrier controls the diffusion of molecules by acting as semipermeable diffusion barriers through the paracellular pathway. It has been reported that transmembrane proteins such as claudin and occludin are essential for the regulation of paracellular permeability (Balda & Matter, 2000;Lee, 2015;Roehlen et al, 2020). ZO-1 is also responsible for the regulation of paracellular permeability (i.e.…”