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miR-122 在微囊藻氨酸-亮氨酸-精氨酸诱导的小鼠肝铁稳态失调中的作用。

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

机构信息

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.

出版信息

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

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.

摘要

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。

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