Knockdown of ARHGDIB promotes autophagy and reduces inflammation in LPS-induced alveolar epithelial cells via the PRKACB/NF-κB pathway.

IF 2.1 4区 医学 Q3 ALLERGY
Allergologia et immunopathologia Pub Date : 2025-09-01 eCollection Date: 2025-01-01 DOI:10.15586/aei.v53i5.1362
Haizhen Jin, Shuangxia Dong, Zhihui Li, Dai Xinjian
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引用次数: 0

Abstract

Background: Acute lung injury (ALI) is a critical clinical condition with high mortality, necessitating the development of more effective therapeutic strategies. Rho Guanine nucleotide dissociation inhibitor (GDP) beta (ARHGDIB) has been shown to exert protective effects against noxious stimuli in various disease models.

Objective: In this study, we investigated whether ARHGDIB knockdown had a protective effect on lipopolysaccharide (LPS)-induced injury in alveolar epithelial cells and elucidated its underlying molecular mechanisms.

Material and methods: Mouse alveolar epithelial cells that were isolated from the lung of a 5-month-old female mouse (MLE-12) were treated with LPS, followed by ARHGDIB knockdown and overexpression of protein kinase A (PKA)-activated catalytic subunit β (PRKACB). Oxidative stress and apoptosis were assessed, while inflammatory cytokine levels were quantified using enzyme-linked immunosorbent serologic assays. Autophagy and PRKACB/nuclear factor kappa B (NF-κB) pathway activation was evaluated by Western blot analysis. Results: LPS upregulated ARHGDIB expression in alveolar epithelial cells. Silencing ARHGDIB significantly reduced oxidative stress inflammation, and promoted autophagy in LPS-treated MLE-12 cells. ARHGDIB knockdown modulated the PRKACB/NF-κB signaling pathway, thereby promoting autophagy and alleviating LPS-induced cellular injury.

Conclusion: This regulatory mechanism significantly reduced oxidative stress and inflammatory responses in alveolar epithelial cells, highlighting the protective role of ARHGDIB silencing in LPS-induced lung injury.

敲低ARHGDIB可通过PRKACB/NF-κB途径促进lps诱导的肺泡上皮细胞自噬并减轻炎症。
背景:急性肺损伤(ALI)是一种死亡率高的危重临床疾病,需要开发更有效的治疗策略。Rho鸟嘌呤核苷酸解离抑制剂(GDP) β (ARHGDIB)在多种疾病模型中显示出对有害刺激的保护作用。目的:在本研究中,我们研究了ARHGDIB基因敲低是否对脂多糖(LPS)诱导的肺泡上皮细胞损伤具有保护作用,并阐明其潜在的分子机制。材料和方法:从5月龄雌性小鼠(MLE-12)的肺中分离小鼠肺泡上皮细胞,用LPS处理,然后敲低ARHGDIB并过表达蛋白激酶a (PKA)激活的催化亚基β (PRKACB)。评估氧化应激和细胞凋亡,同时使用酶联免疫吸附血清学测定炎症细胞因子水平。Western blot检测细胞自噬及PRKACB/核因子κB (NF-κB)通路活化情况。结果:LPS上调肺泡上皮细胞ARHGDIB的表达。沉默ARHGDIB可显著降低lps处理的MLE-12细胞的氧化应激炎症,并促进自噬。ARHGDIB下调可调节PRKACB/NF-κB信号通路,从而促进自噬,减轻lps诱导的细胞损伤。结论:该调节机制显著降低了肺泡上皮细胞的氧化应激和炎症反应,突出了ARHGDIB沉默在lps诱导的肺损伤中的保护作用。
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
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.
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