HIF1α/miR-146α/TRAF6/NF-κB axis modulates hepatic iron overload-induced inflammation

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-146 alpha/TRAF6/NF-kappa B pathway was validated, and the molecular mechanism of the IO-induced decrease of miR-146 alpha in the liver was studied in vivo and in vitro. The expression of TRAF6/NF-kappa B (p65)-dependent inflammatory factors increased, whereas the expression of miR146 alpha decreased during the IO-induced inflammatory response in the liver. The reduced expression of HNF4 alpha caused by HIF1 alpha and miR-34 alpha may decrease the expression of miR-146 alpha. Overexpression of miR-146 alpha alleviated the hepatic inflammatory response caused by IO. Our findings indicate that miR-146 alpha is a key factor in inducing hepatic IO inflammation, which will be another potential target to prevent IO-induced hepatic damage. (c) 2023 Elsevier Inc. All rights reserved.