Role of microRNA-122 in microcystin-leucine arginine-induced dysregulation of hepatic iron homeostasis in mice

microRNA-122 在微囊藻毒素-亮氨酸-精氨酸诱导的小鼠肝脏铁稳态失调中的作用

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作者:Rui Wang, Xiaohui Liu, Jinxia Wu, Haohao Liu, Wenjun Wang, Xinghai Chen, Le Yuan, Yueqin Wang, Xingde Du, Ya Ma, Michael D Losiewicz, Xiaofeng Zhang, Huizhen Zhang

Abstract

Microcystin-leucine arginine (MC-LR) is a cyclic heptapeptide hepatotoxin produced by cyanobacteria. MicroRNA-122 (miR-122) is specifically expressed in the liver. This study focuses on the role of miR-122 in MC-LR-induced dysregulation of hepatic iron homeostasis in C57BL/6 mice. The thirty mice were randomly divided into five groups (Control, 12.5 μg/kg·BW MC-LR, 25 μg/kg·BW MC-LR, Negative control agomir and 25 μg/kg·BW MC-LR + miR-122 agomir). The results show that MC-LR decreases the expressions of miR-122, Hamp, and its related regulators, while increasing the content of hepatic iron and the expressions of FPN1 and Tmprss6. Furthermore, miR-122 agomir pretreatment improves MC-LR induced dysregulation of hepatic iron homeostasis by arousing the related regulators and reducing the expression of Tmprss6. These results suggest that miR-122 agomir can prevent the accumulation of hepatic iron induced by MC-LR, which may be related to the regulation of hepcidin by BMP/SMAD and IL-6/STAT signaling pathways.

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