Wenjun Wang, Jiayi Chen, Songqing Lai, Ruiyuan Zeng, Ming Fang, Li Wan, Yiying Li
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引用次数: 0
Abstract
Thoracic aortic aneurysm (TAA) is a vascular disease associated with high mortality rates. Ferroptosis has been shown to mediate the transformation of vascular smooth muscle cells (VSMCs). However, the regulatory mechanisms by which ferroptosis influences TAA remain unclear. In this study, we induced TAA mouse models using angiotensin II (Ang II) and evaluated the impact of ferroptosis on the pathological changes observed in TAA mice, employing liproxstatin-1 as a treatment. Additionally, we assessed the regulatory effect of METTL14 on the ferroptosis of VSMCs after treating them with ferroptosis activator (IKE). RNA binding protein immunoprecipitation (RIP) and RNA pull-down assays were conducted to investigate the interaction between ACSL4 mRNA and the proteins METTL14 or IGF2BP2. The results indicated that the level of ferroptosis was elevated in the thoracic aorta of TAA mice, and METTL14 was upregulated in TAA models and IKE-induced VSMCs. Knockdown of METTL14 was found to inhibit the progression of TAA by reducing the ferroptosis of VSMCs. Furthermore, IGF2BP2 recognized METTL14-modified ACSL4 mRNA and regulated its stability, thereby mediating the ferroptosis of VSMCs. Collectively, the effects of METTL14 on VSMC ferroptosis present therapeutic potential for the treatment of TAA.
期刊介绍:
The American Journal of Physiology-Cell Physiology is dedicated to innovative approaches to the study of cell and molecular physiology. Contributions that use cellular and molecular approaches to shed light on mechanisms of physiological control at higher levels of organization also appear regularly. Manuscripts dealing with the structure and function of cell membranes, contractile systems, cellular organelles, and membrane channels, transporters, and pumps are encouraged. Studies dealing with integrated regulation of cellular function, including mechanisms of signal transduction, development, gene expression, cell-to-cell interactions, and the cell physiology of pathophysiological states, are also eagerly sought. Interdisciplinary studies that apply the approaches of biochemistry, biophysics, molecular biology, morphology, and immunology to the determination of new principles in cell physiology are especially welcome.