Recent Progress of Ferroptosis in Lung Diseases

Ferroptosis is a new form of programmed cell death due to iron-dependent excess accumulation of lipid peroxides and differs from other programmed cell deaths in morphological and biochemical characteristics. The process of ferroptosis is precisely regulated by iron metabolism, lipid metabolism, amino acid metabolism, and numerous signaling pathways, and plays a complex role in many pathophysiological processes. Recent studies have found that ferroptosis is closely associated with the development and progression of many lung diseases, including acute lung injury, pulmonary ischemia-reperfusion injury, lung cancer, chronic obstructive pulmonary disease, and pulmonary fibrosis. Here, we present a review of the main regulatory mechanisms of ferroptosis and its research progress in the pathogenesis and treatment of lung diseases, with the aim of providing new ideas for basic and clinical research of lung-related diseases.

Dexmedetomidine alleviates pulmonary ischemia-reperfusion injury through modulating the miR-21-5p/Nr4a1 signaling pathway

This study aims to investigate the protection of dexmedetomidine (Dex) against pulmonary ischemia-reperfusion injury (PIRI) in the mouse model and reveal the mechanism in hypoxia reoxygenation (H/R)-induced mouse pulmonary vascular endothelial cells (MPVECs). The lung wet-to-dry weight ratio, histopathological features, and malondialdehyde (MDA) concentrations were measured. The H/R-induced MPVECs were exposed to Dex, and the cell viability, cell apoptosis and protein expressions were assessed by the Cell Counting Kit-8 (CCK8) assay, flow cytometry and western blot, respectively. In addition, the regulatory relationship between miR-21-5p and orphan nuclear receptor 4A1 (Nr4a1) was revealed by several assays, including the dual-luciferase reporter assay, real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. We found that the Dex treatment significantly alleviated pulmonary injury and decreased the level of MDA and wet/dry weight ratio in PIRI mice. Dex treatment also increased cell viability, reduced apoptotic ratio and downregulated expression levels of Cleaved Caspase-3 and Cleaved Caspase-9 in H/R induced MPVECs. Furthermore, the expression of miR-21-5p was upregulated, while Nr4a1 was downregulated by Dex in a concentration-dependent manner in H/R induced MPVECs. Moreover, Nr4a1 was verified as a target of miR-497-5p. Overexpression of Nr4a1 could reverse the protective effects of Dex on alleviating H/R-induced injury in MPVECs. Taken together, Dex treatment attenuated ischemia-reperfusion induced pulmonary injury through modulating the miR-21-5p/Nr4a1 signaling pathway.