College of Public Health, Zhengzhou University, Zhengzhou, People's Republic of China.
School of Basic Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China.
Environ Toxicol. 2020 Aug;35(8):822-830. doi: 10.1002/tox.22918. Epub 2020 Mar 14.
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.
微囊藻毒素-亮氨酸精氨酸(MC-LR)是一种由蓝藻产生的环状七肽肝毒素。微小 RNA-122(miR-122)特异性表达于肝脏。本研究旨在探讨 miR-122 在 MC-LR 诱导的 C57BL/6 小鼠肝铁稳态失调中的作用。将 30 只小鼠随机分为五组(对照组、12.5μg/kg·BW MC-LR 组、25μg/kg·BW MC-LR 组、阴性对照 agomir 组和 25μg/kg·BW MC-LR+miR-122 agomir 组)。结果表明,MC-LR 降低了 miR-122、Hamp 及其相关调节因子的表达,同时增加了肝铁含量和 FPN1、Tmprss6 的表达。此外,miR-122 agomir 预处理通过激活相关调节因子和降低 Tmprss6 的表达,改善了 MC-LR 诱导的肝铁稳态失调。这些结果表明,miR-122 agomir 可以阻止 MC-LR 诱导的肝铁蓄积,这可能与 BMP/SMAD 和 IL-6/STAT 信号通路对铁调素的调节有关。