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p14ARF ameliorates inflammation and airway remodeling in nitric acid aerosol inhalation-induced bronchiolitis obliterans.
Yang, Ting; Xu, Chang; Ding, Niu; Luo, Shujuan; Wu, Bichen; Jin, Shijie; Chen, Yanping.
Afiliação
  • Yang T; Department of Respiratory Medicine, Hunan Children's Hospital, Changsha, China.
Exp Lung Res ; 49(1): 27-38, 2023.
Article em En | MEDLINE | ID: mdl-36621972
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-ß (TGF-ß) 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-ß 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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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Bronquiolite Obliterante / Metaloproteinase 2 da Matriz Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Bronquiolite Obliterante / Metaloproteinase 2 da Matriz Idioma: En Ano de publicação: 2023 Tipo de documento: Article