Key Laboratory of Enviromental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang 550025, Guizhou, PR China.
Guiyang Maternity and Child Health Hospital, Guizhou, PR China.
Ecotoxicol Environ Saf. 2022 Sep 15;243:113990. doi: 10.1016/j.ecoenv.2022.113990. Epub 2022 Aug 20.
Arsenic (As) is a natural hepatotoxicity inducer that is ubiquitous in water, soil, coal, and food. Studies have found that arsenite exposure elicits increased mRNA transcription and decreased protein expression of SOD1 in vivo and in vitro; however, the specific mechanisms remain unclear. Here, we established a model of arsenic-induced chronic liver injury by providing rats with drinking water containing different concentrations of sodium arsenite (NaAsO) and found that NaAsO exposure decreased the mRNA and protein levels of AUF1 and the protein level of SOD1 and elevated the mRNA and protein levels of Dicer1 and miR-155 and the mRNA level of SOD1. Overexpression of AUF1 under NaAsO stress in vitro induced Dicer1 mRNA and protein expression and decreased miR-155 levels, which could be reversed by AUF1 siRNA. In addition, miR-155 overexpression downregulated SOD1 mRNA and protein levels, although this change was inhibited after transfection with an miR-155 inhibitor. Taken together, our findings showed that NaAsO could upregulate Dicer1 mRNA and protein, thereby increasing miR-155 expression by downregulating AUF1 mRNA and protein expression. A dual-luciferase reporter assay indicated that miR-155 decreased the mRNA and protein levels of SOD1 by targeting the SOD1 3'UTR, resulting in liver injury. This study provides an important research basis for further understanding the factors underlying arsenic-induced liver injury to improve the prevention and control strategies for arsenism.
砷（As）是一种天然的肝毒性诱导剂，普遍存在于水、土壤、煤和食物中。研究发现，亚砷酸盐暴露在体内和体外均会引起 SOD1 的 mRNA 转录增加和蛋白表达减少；然而，具体机制尚不清楚。在这里，我们通过给大鼠提供含有不同浓度的亚砷酸钠（NaAsO）的饮用水建立了一个砷诱导的慢性肝损伤模型，发现 NaAsO 暴露降低了 AUF1 的 mRNA 和蛋白水平以及 SOD1 的蛋白水平，同时升高了 Dicer1 和 miR-155 的 mRNA 和蛋白水平以及 SOD1 的 mRNA 水平。体外 NaAsO 应激下 AUF1 的过表达诱导了 Dicer1 的 mRNA 和蛋白表达，并降低了 miR-155 的水平，而 AUF1 siRNA 可逆转这一变化。此外，miR-155 的过表达下调了 SOD1 的 mRNA 和蛋白水平，尽管这种变化在转染 miR-155 抑制剂后被抑制。总之，我们的研究结果表明，NaAsO 可以上调 Dicer1 的 mRNA 和蛋白，从而通过下调 AUF1 的 mRNA 和蛋白表达来增加 miR-155 的表达。双荧光素酶报告基因检测表明，miR-155 通过靶向 SOD1 3'UTR 降低了 SOD1 的 mRNA 和蛋白水平，导致肝损伤。本研究为进一步了解砷诱导肝损伤的相关因素提供了重要的研究基础，有助于改善砷中毒的预防和控制策略。
