CD147 induces asthmatic airway remodeling and activation of circulating fibrocytes in a mouse model of asthma

Abstract Background Airway remodeling is a poorly reversible feature of asthma which lacks effective therapeutic interventions. CD147 can regulate extracellular matrix (ECM) remodeling and tissue fibrosis, and participate in the pathogenesis of asthma. In this study, the role of CD147 in airway remo...

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Main Authors: Zhao Li, Tao Cheng, Yaning Guo, Rong Gao, Xuankun Ma, Xuecong Mao, Xinpeng Han
Format: Article
Language:English
Published: BMC 2024-01-01
Series:Respiratory Research
Subjects:
Online Access:https://doi.org/10.1186/s12931-023-02646-5
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author Zhao Li
Tao Cheng
Yaning Guo
Rong Gao
Xuankun Ma
Xuecong Mao
Xinpeng Han
author_facet Zhao Li
Tao Cheng
Yaning Guo
Rong Gao
Xuankun Ma
Xuecong Mao
Xinpeng Han
author_sort Zhao Li
collection DOAJ
description Abstract Background Airway remodeling is a poorly reversible feature of asthma which lacks effective therapeutic interventions. CD147 can regulate extracellular matrix (ECM) remodeling and tissue fibrosis, and participate in the pathogenesis of asthma. In this study, the role of CD147 in airway remodeling and activation of circulating fibrocytes was investigated in asthmatic mice. Methods Asthmatic mouse model was established by sensitizing and challenging mice with ovalbumin (OVA), and treated with anti-CD147 or Isotype antibody. The number of eosinophils in bronchoalveolar lavage fluid (BALF) was examined by microscope, and the levels of interleukin-4 (IL-4), IL-5 and IL-13 in BALF were detected by enzyme-linked immunosorbent assay (ELISA). The number of CD45+ and collagen I (COL-I)+ circulating fibrocytes in BALF was detected by flow cytometry. Lung tissue sections were respectively stained with hematoxylin and eosin (HE), periodic acid-Schiff (PAS) or Masson trichrome staining, or used for immunohistochemistry of CD31 and immunohistofluorescence of α-smooth muscle actin (α-SMA), CD45 and COL-I. The protein expression of α-SMA, vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), Fibronectin, and COL-I was determined by western blotting. Results Anti-CD147 treatment significantly reduced the number of eosinophils and the levels of IL-4, IL-13, and IL-5 in BALF, and repressed airway inflammatory infiltration and airway wall thickening in asthmatic mice. Anti-CD147 treatment also reduced airway goblet cell metaplasia, collagen deposition, and angiogenesis in asthmatic mice, accompanied by inhibition of VEGF and α-SMA expression. The number of CD45+COL-I+ circulating fibrocytes was increased in BALF and lung tissues of OVA-induced asthmatic mice, but was decreased by anti-CD147 treatment. In addition, anti-CD147 treatment also reduced the protein expression of COL-I, fibronectin, and TGF-β1 in lung tissues of asthmatic mice. Conclusion OVA-triggered airway inflammation and airway remodeling in asthmatic mice can be repressed by anti-CD147 treatment, along with inhibiting the accumulation and activation of circulating fibrocytes.
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spelling doaj.art-a675517dfbb342dfa1896ea57607be6e2024-01-07T12:41:16ZengBMCRespiratory Research1465-993X2024-01-012511910.1186/s12931-023-02646-5CD147 induces asthmatic airway remodeling and activation of circulating fibrocytes in a mouse model of asthmaZhao Li0Tao Cheng1Yaning Guo2Rong Gao3Xuankun Ma4Xuecong Mao5Xinpeng Han6Department of Cardiopulmonary Diseases, Xi ’an International Medical Center HospitalDepartment of Cardiopulmonary Diseases, Xi ’an International Medical Center HospitalDepartment of Cardiopulmonary Diseases, Xi ’an International Medical Center HospitalDepartment of Cardiopulmonary Diseases, Xi ’an International Medical Center HospitalDepartment of Cardiopulmonary Diseases, Xi ’an International Medical Center HospitalDepartment of Cardiopulmonary Diseases, Xi ’an International Medical Center HospitalDepartment of Cardiopulmonary Diseases, Xi ’an International Medical Center HospitalAbstract Background Airway remodeling is a poorly reversible feature of asthma which lacks effective therapeutic interventions. CD147 can regulate extracellular matrix (ECM) remodeling and tissue fibrosis, and participate in the pathogenesis of asthma. In this study, the role of CD147 in airway remodeling and activation of circulating fibrocytes was investigated in asthmatic mice. Methods Asthmatic mouse model was established by sensitizing and challenging mice with ovalbumin (OVA), and treated with anti-CD147 or Isotype antibody. The number of eosinophils in bronchoalveolar lavage fluid (BALF) was examined by microscope, and the levels of interleukin-4 (IL-4), IL-5 and IL-13 in BALF were detected by enzyme-linked immunosorbent assay (ELISA). The number of CD45+ and collagen I (COL-I)+ circulating fibrocytes in BALF was detected by flow cytometry. Lung tissue sections were respectively stained with hematoxylin and eosin (HE), periodic acid-Schiff (PAS) or Masson trichrome staining, or used for immunohistochemistry of CD31 and immunohistofluorescence of α-smooth muscle actin (α-SMA), CD45 and COL-I. The protein expression of α-SMA, vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), Fibronectin, and COL-I was determined by western blotting. Results Anti-CD147 treatment significantly reduced the number of eosinophils and the levels of IL-4, IL-13, and IL-5 in BALF, and repressed airway inflammatory infiltration and airway wall thickening in asthmatic mice. Anti-CD147 treatment also reduced airway goblet cell metaplasia, collagen deposition, and angiogenesis in asthmatic mice, accompanied by inhibition of VEGF and α-SMA expression. The number of CD45+COL-I+ circulating fibrocytes was increased in BALF and lung tissues of OVA-induced asthmatic mice, but was decreased by anti-CD147 treatment. In addition, anti-CD147 treatment also reduced the protein expression of COL-I, fibronectin, and TGF-β1 in lung tissues of asthmatic mice. Conclusion OVA-triggered airway inflammation and airway remodeling in asthmatic mice can be repressed by anti-CD147 treatment, along with inhibiting the accumulation and activation of circulating fibrocytes.https://doi.org/10.1186/s12931-023-02646-5AsthmaCD147Airway remodelingCirculating fibrocytes
spellingShingle Zhao Li
Tao Cheng
Yaning Guo
Rong Gao
Xuankun Ma
Xuecong Mao
Xinpeng Han
CD147 induces asthmatic airway remodeling and activation of circulating fibrocytes in a mouse model of asthma
Respiratory Research
Asthma
CD147
Airway remodeling
Circulating fibrocytes
title CD147 induces asthmatic airway remodeling and activation of circulating fibrocytes in a mouse model of asthma
title_full CD147 induces asthmatic airway remodeling and activation of circulating fibrocytes in a mouse model of asthma
title_fullStr CD147 induces asthmatic airway remodeling and activation of circulating fibrocytes in a mouse model of asthma
title_full_unstemmed CD147 induces asthmatic airway remodeling and activation of circulating fibrocytes in a mouse model of asthma
title_short CD147 induces asthmatic airway remodeling and activation of circulating fibrocytes in a mouse model of asthma
title_sort cd147 induces asthmatic airway remodeling and activation of circulating fibrocytes in a mouse model of asthma
topic Asthma
CD147
Airway remodeling
Circulating fibrocytes
url https://doi.org/10.1186/s12931-023-02646-5
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