Overexpression of USP8 inhibits inflammation and ferroptosis in chronic obstructive pulmonary disease by regulating the OTUB1/SLC7A11 signaling pathway.

IF 2.5 4区医学 Q3 ALLERGY Allergologia et immunopathologia Pub Date : 2024-07-01 eCollection Date: 2024-01-01 DOI:10.15586/aei.v52i4.1108

Lu Liu, Yu Zhang, Di Xu, Dan Zhu, Ying Zhou, Zhihai Chen, Xiufeng Huang

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Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a familiar disease, and owns high morbidity and mortality, which critically damages the health of patients. Ubiquitin-specific peptidase 8 (USP8) is a pivotal protein to join in the regulation of some diseases. In a previous report, it was determined that USP8 expression is down-regulated in LPS-treated BEAS-2B cells, and USP8 restrains inflammatory response and accelerates cell viability. However, the regulatory roles of USP8 on ferroptosis in COPD are rarely reported, and the associated molecular mechanisms keep vague.

Objective: To investigate the regulatory functions of USP8 in COPD progression.

Material and methods: The lung functions were measured through the Buxco Fine Pointe Series Whole Body Plethysmography (WBP). The Fe level was tested through the Fe assay kit. The protein expressions were assessed through western blot. The levels of tumor necrosis -factor-α, interleukin 6, and interleukin 8 were evaluated through enzyme-linked immunosorbent serologic assay. Cell viability was tested through CCK-8 assay.

Results: In this work, it was discovered that overexpression of USP8 improved lung function in COPD mice. In addition, overexpression of USP8 repressed ferroptosis by regulating glutathione peroxidase 4 and acyl-CoA synthetase long-chain family 4 expressions in COPD mice. Overexpression of USP8 suppressed inflammation in COPD mice. Furthermore, overexpression of USP8 suppressed ferroptosis in COPD cell model. At last, it was verified that overexpression of USP8 accelerated ubiquitin aldehyde-binding protein 1 (OTUB1)/solute carrier family 7 member 11 (SLC7A11) pathway.

Conclusion: This study manifested that overexpression of USP8 restrained inflammation and ferroptosis in COPD by regulating the OTUB1/SLC7A11 signaling pathway. This discovery hinted that USP8 could be a potential target for COPD treatment.

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过表达 USP8 可通过调节 OTUB1/SLC7A11 信号通路抑制慢性阻塞性肺病的炎症和铁变态反应。

背景：慢性阻塞性肺疾病（COPD）是一种常见疾病，发病率和死亡率都很高，严重损害了患者的健康。泛素特异性肽酶 8（USP8）是参与调控某些疾病的关键蛋白。之前的一项研究发现，USP8 在 LPS 处理的 BEAS-2B 细胞中表达下调，USP8 可抑制炎症反应并加速细胞存活。然而，USP8 在慢性阻塞性肺病中对铁变态反应的调控作用却鲜有报道，相关的分子机制也一直模糊不清：材料与方法：材料：通过 Buxco Fine Pointe 系列全身胸透仪（WBP）测量肺功能。通过铁测定试剂盒检测铁水平。蛋白质表达通过 Western 印迹进行评估。肿瘤坏死因子-α、白细胞介素 6 和白细胞介素 8 的水平通过酶联免疫吸附血清测定法进行评估。通过 CCK-8 法检测细胞活力：结果：这项研究发现，过表达 USP8 可改善慢性阻塞性肺病小鼠的肺功能。此外，通过调节谷胱甘肽过氧化物酶 4 和酰基-CoA 合成酶长链家族 4 的表达，过表达 USP8 可抑制 COPD 小鼠的铁变态反应。过表达 USP8 可抑制 COPD 小鼠的炎症反应。此外，USP8 的过表达抑制了 COPD 细胞模型中的铁变态反应。最后，研究验证了过表达 USP8 会加速泛素醛结合蛋白 1（OTUB1）/绝对载体家族 7 成员 11（SLC7A11）通路的形成：本研究表明，过表达 USP8 可通过调节 OTUB1/SLC7A11 信号通路抑制慢性阻塞性肺病的炎症和铁变态反应。这一发现提示 USP8 可能是治疗慢性阻塞性肺病的潜在靶点。

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

Allergologia et immunopathologia 医学-过敏

CiteScore

3.70

自引率

0.00%

发文量

131

审稿时长

6-12 weeks

期刊介绍： Founded in 1972 by Professor A. Oehling, Allergologia et Immunopathologia is a forum for those working in the field of pediatric asthma, allergy and immunology. Manuscripts related to clinical, epidemiological and experimental allergy and immunopathology related to childhood will be considered for publication. Allergologia et Immunopathologia is the official journal of the Spanish Society of Pediatric Allergy and Clinical Immunology (SEICAP) and also of the Latin American Society of Immunodeficiencies (LASID). It has and independent international Editorial Committee which submits received papers for peer-reviewing by international experts. The journal accepts original and review articles from all over the world, together with consensus statements from the aforementioned societies. Occasionally, the opinion of an expert on a burning topic is published in the "Point of View" section. Letters to the Editor on previously published papers are welcomed. Allergologia et Immunopathologia publishes 6 issues per year and is included in the major databases such as Pubmed, Scopus, Web of Knowledge, etc.