Inhibiting fatty acid-binding protein 4 reverses inflammation and apoptosis in wasp sting-induced acute kidney injury

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology Pub Date : 2025-04-02 DOI:10.1016/j.fct.2025.115428

Ling Li , Hai Yuan , Haoran Li , Rui Cheng , Zilin Zhou , Fengqi Hu , Liang Xu

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引用次数: 0

Abstract

Fatty acid-binding protein 4 (FABP4) has been implicated in the pathogenesis of several forms of acute kidney injury (AKI), including rhabdomyolysis, ischemia/reperfusion, sepsis, and cisplatin-induced AKI. However, whether FABP4 inhibition confers a renoprotective effect in wasp sting-induced AKI remains unclear. Therefore, in this study, we investigated the role of FABP4 in wasp sting-induced AKI in vivo and in vitro. We assessed renal dysfunction, mitochondrial injury, cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) signaling pathway-mediated inflammation, and apoptosis. FABP4 expression was significantly higher in wasp sting-induced models of AKI than in the control groups, and pharmacological inhibition of FABP4 attenuated renal dysfunction and tubular injury. Wasp sting-induced AKI was associated with mitochondrial damage induced by excessive mitochondrial fission, which was effectively mitigated by FABP4 inhibition. The FABP4 inhibitor reduced the release of mitochondrial DNA (mtDNA) and cytochrome c (Cyt-c) from damaged mitochondria. cGAS–STING activation induced by mtDNA was downregulated by FABP4 inhibition. Subsequently, inflammation and apoptosis in wasp sting-induced AKI were significantly alleviated, as evidenced by decreased levels of inflammatory mediators and apoptosis-related proteins. In conclusion, FABP4 was found to play a key role in the occurrence and progression of wasp sting-induced AKI.

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抑制脂肪酸结合蛋白4可逆转黄蜂蜇伤所致急性肾损伤的炎症和细胞凋亡

脂肪酸结合蛋白4 （FABP4）与多种形式的急性肾损伤（AKI）的发病机制有关，包括横纹肌溶解、缺血/再灌注、脓毒症和顺铂诱导的AKI。然而，FABP4抑制是否在黄蜂蜇伤诱导的AKI中具有肾保护作用尚不清楚。因此，在本研究中，我们在体内和体外研究了FABP4在黄蜂蜇伤诱导的AKI中的作用。我们评估了肾功能障碍、线粒体损伤、环GMP-AMP合成酶(cGAS) -干扰素基因刺激因子（STING）信号通路介导的炎症和细胞凋亡。FABP4在黄蜂蜇伤诱导的AKI模型中的表达明显高于对照组，药理抑制FABP4可减轻肾功能障碍和肾小管损伤。黄蜂蜇伤引起的AKI与线粒体过度裂变引起的线粒体损伤有关，而FABP4抑制可有效减轻线粒体损伤。FABP4抑制剂减少线粒体DNA （mtDNA）和细胞色素c （Cyt-c）从受损线粒体的释放。mtDNA诱导的cGAS-STING激活被FABP4抑制下调。随后，黄蜂蜇伤诱导AKI的炎症和凋亡明显减轻，炎症介质和凋亡相关蛋白水平下降。综上所述，我们发现FABP4在黄蜂蜇伤AKI的发生和发展中发挥了关键作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Food and Chemical Toxicology 工程技术-毒理学

CiteScore

10.90

自引率

4.70%

发文量

651

审稿时长

31 days

期刊介绍： Food and Chemical Toxicology (FCT), an internationally renowned journal, that publishes original research articles and reviews on toxic effects, in animals and humans, of natural or synthetic chemicals occurring in the human environment with particular emphasis on food, drugs, and chemicals, including agricultural and industrial safety, and consumer product safety. Areas such as safety evaluation of novel foods and ingredients, biotechnologically-derived products, and nanomaterials are included in the scope of the journal. FCT also encourages submission of papers on inter-relationships between nutrition and toxicology and on in vitro techniques, particularly those fostering the 3 Rs. The principal aim of the journal is to publish high impact, scholarly work and to serve as a multidisciplinary forum for research in toxicology. Papers submitted will be judged on the basis of scientific originality and contribution to the field, quality and subject matter. Studies should address at least one of the following: -Adverse physiological/biochemical, or pathological changes induced by specific defined substances -New techniques for assessing potential toxicity, including molecular biology -Mechanisms underlying toxic phenomena -Toxicological examinations of specific chemicals or consumer products, both those showing adverse effects and those demonstrating safety, that meet current standards of scientific acceptability. Authors must clearly and briefly identify what novel toxic effect (s) or toxic mechanism (s) of the chemical are being reported and what their significance is in the abstract. Furthermore, sufficient doses should be included in order to provide information on NOAEL/LOAEL values.