Effects of acute and chronic disease on cell junctions in mouse liver.

Abstract

Cell junctions, including anchoring, occluding and communicating junctions, play an indispensable role in tissue architecture and homeostasis. Consequently, malfunctioning of cell junctions is linked with a wide range of disorders, including in liver. The present study was set up to investigate the effects of acute and chronic disease induced by chemical compounds on hepatic cell junctions in mice. Mice were either overdosed with paracetamol or repeatedly administered carbon tetrachloride followed by sampling at 24 hours or 8 weeks, respectively. mRNA and protein expression levels of adherens, gap and tight junction components were measured in liver using reverse transcription quantitative real-time polymerase chain reaction analysis and immunoblot techniques, respectively. It was found that protein levels of the adherens junction building blocks β-catenin and γ-catenin, the gap junction components Cx26 and Cx32, and the tight junction constituent zonula occludens 2 were decreased, while mRNA levels of the adherens junction building block E-cadherin, and the tight junction constituent zonula occludens 2 and claudin 1 were upregulated following paracetamol overdosing. Repeated administration of carbon tetrachloride increased protein levels of E-cadherin, β-catenin, Cx26, Cx32, Cx43 and claudin 1. The latter was reflected at the mRNA level. In conclusion, acute and chronic liver disease have different effects on cell junctions in liver.