Caveolin-1 protects against liver injury and lipid accumulation in alcoholic fatty liver via ferroptosis resistance

IF 3.2 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology Pub Date : 2025-03-11 DOI:10.1016/j.molimm.2025.02.012

Weiju Xue , Ning Guo , Liang Shan , Zhengsheng Zhang , Yuquan Sun , Yong Wang , Xing Fang , Xiuzhen Liu , Jianjun Liu , Chengmu Hu

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引用次数: 0

Abstract

Alcoholic fatty liver (AFL) is one of the most common chronic liver diseases globally with complex and controversial pathogenesis. Recent evidence suggests that iron overload and lipid peroxidation are risk factors for AFL. Caveolin-1 (CAV1) is an important signal platform that can maintain lipid homeostasis during the development of non-alcoholic fatty liver. Here, we studied the effect of CAV1 on ferroptosis in AFL. The AFL mouse model was established by chronic-plus-binge alcohol feeding. In vitro, AML-12 cells were incubated with ethanol and oleic acid for 48 h. We found alcohol-induced AFL triggered ferroptosis and decreased CAV1 expression. Overexpression of CAV1 by CAV1 scaffolding domain peptides (CSD) attenuated liver injury and hepatic steatosis, as well as inhibited ferroptosis in AFL mice. Additionally, the effects of CAV1 on ferroptosis-related protein levels (such as SLC7A11, GPX4, and ACSL4) and lipid accumulation were reversed by its small interfering RNA administration. Ferroptosis agonist (Erastin) treatment abrogated CAV1 plasmid-mediated ferroptosis resistance and steatosis alleviation. Collectively, the results revealed a crucial role of CAV1 in preventing hepatic steatosis and ferroptosis in alcohol-induced liver injury, which may identify potential targets for the treatment of AFL.

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来源期刊

Molecular immunology 医学-免疫学

CiteScore

6.90

自引率

2.80%

发文量

324

审稿时长

50 days

期刊介绍： Molecular Immunology publishes original articles, reviews and commentaries on all areas of immunology, with a particular focus on description of cellular, biochemical or genetic mechanisms underlying immunological phenomena. Studies on all model organisms, from invertebrates to humans, are suitable. Examples include, but are not restricted to: Infection, autoimmunity, transplantation, immunodeficiencies, inflammation and tumor immunology Mechanisms of induction, regulation and termination of innate and adaptive immunity Intercellular communication, cooperation and regulation Intracellular mechanisms of immunity (endocytosis, protein trafficking, pathogen recognition, antigen presentation, etc) Mechanisms of action of the cells and molecules of the immune system Structural analysis Development of the immune system Comparative immunology and evolution of the immune system "Omics" studies and bioinformatics Vaccines, biotechnology and therapeutic manipulation of the immune system (therapeutic antibodies, cytokines, cellular therapies, etc) Technical developments.