Cholestasis Differentially Affects Liver Connexins

Cholestasis Differentially Affects Liver Connexins
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DOI:
10.3390/ijms21186534
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发表时间:
2020-09-01
影响因子:
5.6
通讯作者:
Vinken, Mathieu
Vinken, Mathieu
中科院分区:
生物学2区
文献类型:
--
作者:
Cooreman, Axelle;Van Campenhout, Raf;Vinken, Mathieu

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连接蛋白是组织稳态的目标保持者,包括在肝脏中。因此,他们经常参与疾病。本研究旨在研究胆汁淤积性疾病对肝脏中连接蛋白26、连接蛋白32和连接蛋白43产生的影响。为此目的,胆管结扎,一个众所周知的触发胆汁淤积性肝损伤,适用于小鼠。同时,将人肝癌HepaRG细胞培养物暴露于胆汁淤积药物和胆汁酸。随后对来自体内和体外环境的样品进行mRNA和蛋白质量的评估以及原位免疫染色。虽然胆汁淤积对连接蛋白26和连接蛋白43的结果在实验环境中不同,但对连接蛋白32观察到更广泛的抑制作用。这也在许多其他肝脏病理中观察到,并可能表明连接蛋白32作为肝脏疾病和毒性的稳健生物标志物的作用。
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.