Mo Fengfeng, Tang Yuxiao, Shen Hui, Wu Lusha, Liu Qing, Nie Shuang, Li Min, Ling Chen
Department of Naval Nutrition and Food Hygiene, Faculty of Naval Medicine, Naval Medical University, Shanghai, China.
Department of Naval Nutrition and Food Hygiene, Faculty of Naval Medicine, Naval Medical University, Shanghai, China; Institute of International Medical Science and Technology, Sanda University, Shanghai, China.
J Nutr Biochem. 2024 Mar;125:109499. doi: 10.1016/j.jnutbio.2023.109499. Epub 2023 Oct 22.
Transfusional therapy is used to cure anemia but raises the risk of hepatic iron overload (IO), which triggers oxidative stress damage, inflammation, and failure even fibrosis. microRNAs play a vital role in developing hepatic diseases. This study presented the mechanism by which IO induce hepatic inflammation through microRNAs. In this study, microRNA expression profiling in the liver was observed after IO for 2 weeks, in which the target microRNA will be found. IO activating the miR-146α/TRAF6/NF-κB pathway was validated, and the molecular mechanism of the IO-induced decrease of miR-146α in the liver was studied in vivo and in vitro. The expression of TRAF6/NF-κB (p65)-dependent inflammatory factors increased, whereas the expression of miR-146α decreased during the IO-induced inflammatory response in the liver. The reduced expression of HNF4α caused by HIF1α and miR-34α may decrease the expression of miR-146α. Overexpression of miR-146α alleviated the hepatic inflammatory response caused by IO. Our findings indicate that miR-146α is a key factor in inducing hepatic IO inflammation, which will be another potential target to prevent IO-induced hepatic damage.
输血疗法用于治疗贫血，但会增加肝脏铁过载（IO）的风险，而肝脏铁过载会引发氧化应激损伤、炎症甚至肝衰竭及纤维化。微小RNA在肝脏疾病的发展过程中起着至关重要的作用。本研究揭示了铁过载通过微小RNA诱导肝脏炎症的机制。在本研究中，观察了铁过载2周后肝脏中的微小RNA表达谱，从中找出靶微小RNA。验证了铁过载激活miR-146α/TRAF6/NF-κB通路，并在体内和体外研究了铁过载导致肝脏中miR-146α减少的分子机制。在铁过载诱导的肝脏炎症反应过程中，TRAF6/NF-κB（p65）依赖性炎症因子的表达增加，而miR-146α的表达降低。HIF1α和miR-34α导致的肝细胞核因子4α（HNF4α）表达降低可能会使miR-146α的表达减少。miR-146α的过表达减轻了铁过载引起的肝脏炎症反应。我们的研究结果表明，miR-146α是诱导肝脏铁过载炎症的关键因素，这将是预防铁过载诱导的肝损伤的另一个潜在靶点。
