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. 2020 Aug;35(8):822-830.
doi: 10.1002/tox.22918. Epub 2020 Mar 14.

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

Rui Wang  1 , Xiaohui Liu  2 , Jinxia Wu  1 , Haohao Liu  1 , Wenjun Wang  3 , Xinghai Chen  4 , Le Yuan  1 , Yueqin Wang  1 , Xingde Du  1 , Ya Ma  1 , Michael D Losiewicz  4 , Xiaofeng Zhang  1 , Huizhen Zhang  1
Affiliations

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

Rui Wang et al. Environ Toxicol. 2020 Aug.

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.

Keywords: C57BL/6 mice; MC-LR; hepcidin; iron homeostasis; microRNA-122.

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