HAVcR-1 reduces the integrity of human endothelial tight junctions.

Background: Hepatitis A virus cellular receptor-1 (HAVcR-1) is the cellular receptor for Hepatotropic picornavirus. Although HAVcR-1 is expressed in every human organ, its natural function remains unknown. This study investigated the location, association and functionality of HAVcR-1 in human endothelial cells. Materials and Methods: HAVcR-1 was either overexpressed or knocked-down by plasmid electroporation in human umbilical vein endothelial (HECV) cells. Changes in tight junction (TJ) behaviour were assessed using transendothelial resistance, and paracellular permeability. Binding partners and the location of HAVcR-1 protein was assessed using Western blotting/immunofluorescence. Results: HAVcR-1 co-localised with zonula occludens-1 (ZO-1) and ZO-2 proteins, both of which are involved in the formation, maintenance and function of TJ. The overexpression of HAVcR-1 resulted in reduced TJ formation; knockdown cells were resistant to hepatocyte growth factor (HGF)-mediated TJ disruption. HGF was unable to effect reduced resistance in these cells. HAVcR-1 was co-precipitated with the TJ regulatory factor Ras homolog gene family, member C (Rho C). Conclusion: HAVcR-1 may have a novel function as part of the regulatory apparatus for TJ in human endothelial cells.