p14ARF ameliorates inflammation and airway remodeling in nitric acid aerosol inhalation-induced bronchiolitis obliterans.

IF 1.5 4区医学 Q3 RESPIRATORY SYSTEM

Experimental Lung Research Pub Date : 2023-01-01 DOI:10.1080/01902148.2022.2163322

Ting Yang, Chang Xu, Niu Ding, Shujuan Luo, Bichen Wu, Shijie Jin, Yanping Chen

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引用次数: 0

Abstract

Background: To investigate the protective effect of p14ARF in a nitric acid (NA) aerosol inhalation-induced bronchiolitis obliterans (BO) mouse model and its potential regulatory mechanism.

Methods: A BO mouse model was established by NA aerosol inhalation. The expressions of p14ARF, phosphatidylinositol-3-kinase (PI3K), and protein kinase B (AKT) were detected by quantitative reverse transcription PCR (qRT-PCR) and western blot (WB). Hematoxylin (HE) staining, Masson staining, and periodic acid-Schiff (PAS) staining observed pulmonary histological changes. TdT-mediated dUTP nick end labeling (TUNEL) staining detected pulmonary cell apoptosis, and enzyme-linked immunosorbent assay (ELISA) measured matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), interleukon-6 (IL-6), and transforminh growth factor-β (TGF-β) levels in lung tissue and bronchoalveolar lavage fluid (BALF).

Results: The expressions of p14ARF, PI3K, and AKT showed a time gradient change, with a decrease trend (*P < 0.05 and **P < 0.01). Severe inflammatory infiltration and tracheal fibrosis were found in lung tissue in the modeling group (BO group) compared with the control group (Con group). The pH, PaO₂, and PaO₂/FiO₂ values significantly reduced, while the PaCO₂ value and the number of TUNEL-positive cells increased in BO group (P < 0.05). In addition, MMP-2, MMP-9, IL-6, and TGF-β levels remarkably increased, with an increase in the number of white blood cells, neutrophils, and lymphocytes in BO group (P < 0.05). Furthermore, p14ARF up-regulation reversed the trend of the aforementioned indexes in BO mice.

Conclusions: p14ARF ameliorated the inflammatory response and airway remodeling in a BO mouse model via the PI3K/AKT pathway.

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p14ARF改善硝酸气溶胶吸入致闭塞性细支气管炎的炎症和气道重塑。

背景:探讨p14ARF对硝酸(NA)气溶胶吸入致闭塞性细支气管炎(BO)小鼠模型的保护作用及其可能的调控机制。方法:NA气雾剂吸入建立BO小鼠模型。采用定量反转录PCR (qRT-PCR)和western blot (WB)检测p14ARF、磷脂酰肌醇-3激酶(PI3K)和蛋白激酶B (AKT)的表达。苏木精(HE)染色、马松(Masson)染色和周期性酸-希夫(PAS)染色观察肺组织变化。tdt介导的dUTP nick end labeling (TUNEL)染色检测肺细胞凋亡，酶联免疫吸附试验(ELISA)检测肺组织和支气管肺泡灌洗液(BALF)中基质金属蛋白酶-2 (MMP-2)、MMP-9、组织金属蛋白酶-1抑制剂(TIMP-1)、白细胞介素-6 (IL-6)、转化生长因子-β (TGF-β)水平。结果:BO组p14ARF、PI3K、AKT表达呈时间梯度变化，呈下降趋势(* p2)， PaO2/FiO2值显著降低，PaCO2值和tunel阳性细胞数量增加(P)。结论:p14ARF通过PI3K/AKT通路改善BO小鼠模型的炎症反应和气道重构。

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

Experimental Lung Research 医学-呼吸系统

CiteScore

3.80

自引率

0.00%

发文量

审稿时长

2 months

期刊介绍： Experimental Lung Research publishes original articles in all fields of respiratory tract anatomy, biology, developmental biology, toxicology, and pathology. Emphasis is placed on investigations concerned with molecular, biochemical, and cellular mechanisms of normal function, pathogenesis, and responses to injury. The journal publishes reports on important methodological advances on new experimental modes. Also published are invited reviews on important and timely research advances, as well as proceedings of specialized symposia. Authors can choose to publish gold open access in this journal.