Asthmatic Eosinophils Alter the Gene Expression of Extracellular Matrix Proteins in Airway Smooth Muscle Cells and Pulmonary Fibroblasts.

Autor: Janulaityte I; Laboratory of Pulmonology, Department of Pulmonology, Lithuanian University of Health Sciences, LT-44307 Kaunas, Lithuania., Januskevicius A; Laboratory of Pulmonology, Department of Pulmonology, Lithuanian University of Health Sciences, LT-44307 Kaunas, Lithuania., Rimkunas A; Laboratory of Pulmonology, Department of Pulmonology, Lithuanian University of Health Sciences, LT-44307 Kaunas, Lithuania., Palacionyte J; Department of Pulmonology, Lithuanian University of Health Sciences, LT-44307 Kaunas, Lithuania., Vitkauskiene A; Department of Laboratory Medicine, Lithuanian University of Health Sciences, LT-44307 Kaunas, Lithuania., Malakauskas K; Laboratory of Pulmonology, Department of Pulmonology, Lithuanian University of Health Sciences, LT-44307 Kaunas, Lithuania.; Department of Pulmonology, Lithuanian University of Health Sciences, LT-44307 Kaunas, Lithuania.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2022 Apr 07; Vol. 23 (8). Date of Electronic Publication: 2022 Apr 07.
DOI: 10.3390/ijms23084086
Abstrakt: The impaired production of extracellular matrix (ECM) proteins by airway smooth muscle cells (ASMC) and pulmonary fibroblasts (PF) is a part of airway remodeling in asthma. This process might be influenced by eosinophils that migrate to the airway and abundantly secrete various cytokines, including TGF-β. We aimed to investigate the effect of asthmatic eosinophils on the gene expression of ECM proteins in ASMC and PF. A total of 34 study subjects were recruited: 14 with allergic asthma (AA), 9 with severe non-allergic eosinophilic asthma (SNEA), and 11 healthy subjects (HS). All AA patients underwent bronchial allergen challenge with D. pteronyssinus . The peripheral blood eosinophils were isolated using high-density centrifugation and magnetic separation. The individual cell cultures were made using hTERT ASMC and MRC-5 cell lines and the subjects' eosinophils. The gene expression of ECM and the TGF-β signaling pathway was analyzed using qRT-PCR. We found that asthmatic eosinophils significantly promoted collagen I, fibronectin, versican, tenascin C, decorin, vitronectin, periostin, vimentin, MMP-9, ADAM33, TIMP-1, and TIMP-2 gene expression in ASMC and collagen I, collagen III, fibronectin, elastin, decorin, MMP-2, and TIMP-2 gene expression in PF compared with the HS eosinophil effect. The asthmatic eosinophils significantly increased the gene expression of several canonical and non-canonical TGF-β signaling pathway components in ASMC and PF compared with the HS eosinophil effect. The allergen-activated AA and SNEA eosinophils had a greater effect on these changes. In conclusion, asthmatic eosinophils, especially SNEA and allergen-activated eosinophils, imbalanced the gene expression of ECM proteins and their degradation-regulating proteins. These changes were associated with increased gene expression of TGF-β signaling pathway molecules in ASMC and PF.
Databáze: MEDLINE
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