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

• Published in: International journal of molecular sciences Vol. 23; no. 8; p. 4086
• Main Authors: Janulaityte, Ieva, Januskevicius, Andrius, Rimkunas, Airidas, Palacionyte, Jolita, Vitkauskiene, Astra, Malakauskas, Kestutis
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 07.04.2022; MDPI
• Subjects: ADAM Proteins; Allergens; Allergens - metabolism; Allergies; Animals; Asthma; Asthma - metabolism; Collagen; Collagen - metabolism; Decorin - genetics; Dermatophagoides pteronyssinus - genetics; Eosinophils; Extracellular matrix; Extracellular Matrix - metabolism; Extracellular Matrix Proteins - genetics; Extracellular Matrix Proteins - metabolism; Fibroblasts; Fibroblasts - metabolism; Fibronectins - metabolism; Gene Expression; Homeostasis; Humans; Lung - metabolism; Myocytes, Smooth Muscle - metabolism; Pathogenesis; Proteins; Smooth muscle; Tissue Inhibitor of Metalloproteinase-2 - metabolism; Transforming Growth Factor beta - metabolism; TGF-β signaling pathway; extracellular matrix proteins; airway remodeling; airway smooth muscle cells; allergy; asthma; eosinophil; pulmonary fibroblasts
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23084086

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.