Cholestasis Differentially Affects Liver Connexins

胆汁淤积对肝脏连接蛋白有不同的影响

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作者:Axelle Cooreman, Raf Van Campenhout, Sara Crespo Yanguas, Eva Gijbels, Kaat Leroy, Alanah Pieters, Andrés Tabernilla, Pieter Van Brantegem, Pieter Annaert, Bruno Cogliati, Mathieu Vinken

Abstract

Connexins are goal keepers of tissue homeostasis, including in the liver. As a result, they are frequently involved in disease. The current study was set up to investigate the effects of cholestatic disease on the production of connexin26, connexin32 and connexin43 in the liver. For this purpose, bile duct ligation, a well-known trigger of cholestatic liver injury, was applied to mice. In parallel, human hepatoma HepaRG cell cultures were exposed to cholestatic drugs and bile acids. Samples from both the in vivo and in vitro settings were subsequently subjected to assessment of mRNA and protein quantities as well as to in situ immunostaining. While the outcome of cholestasis on connexin26 and connexin43 varied among experimental settings, a more generalized repressing effect was seen for connexin32. This has also been observed in many other liver pathologies and could suggest a role for connexin32 as a robust biomarker of liver disease and toxicity.

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