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

Abstract

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.

Longitudinal cytokine and multi-modal health data of an extremely severe ME/CFS patient with HSD reveals insights into immunopathology, and disease severity

“…Notably, mast cell activation syndrome (MCAS) is highly prevalent in ME/CFS and connective tissue disorders, including EDS/hEDS/HSD. Additionally, aberrant eosinophil function is commonly observed in connective tissue disorders ( 167 , 168 ) and reported in the context of ME/CFS ( 169 , 170 ). This underscores the necessity for further exploration into the dynamic interactions between mast cell and eosinophil immune responses and connective tissue function in ME/CFS ( Figure 7 ).…”

Serum Proteomic Analysis Revealed Biomarkers for Eosinophilic Chronic Rhinosinusitis with Nasal Polyps Pathophysiology

“… 47 , 48 It was found that MMP2 possessed the capability to enhance the infiltration and aggregation of eosinophils at the inflammation site through its control over the degradation of the extracellular matrix and the dissociation of extracellular matrix molecules. 49 Moreover, a prior study revealed that the increased expression of MMP-2 and MMP13 in allergic nasal mucosa could expedite eosinophil migration to the nasal mucosa among patients with allergic rhinitis. This observation underscored the dynamic participation of MMPs in the pathogenesis of allergic rhinitis.…”

Matrix Metalloproteinases in the Periodontium—Vital in Tissue Turnover and Unfortunate in Periodontitis

“…The ECM (also matrisome) is a complex non-cellular three-dimensional macromolecular network present within all tissues and organs, forming the foundation on which cells sit. It is composed of 1. structural and specialized proteins (such as collagens, elastin, fibrillin, laminin, fibronectin, vitronectin, nidogen also known as entactin, tenascin, amelogenins, dentin sialoprotein, and dentin phosphoprotein), 2. glycosaminoglycans, also known as mucopolysaccharides (hyaluronan, heparin, heparan sulphate, chondroitin sulphate, keratan sulphate, and dermatan sulphate), which are the major components of proteoglycans (proteins that contain covalently linked glycosaminoglycans, such as syndecan, betaglycan, perlecan, aggrecan, decorin, andversican), 3. minerals (hydroxyapatite and derivatives found in bone or dentine), 4. lipids, 5. water, and 6. tissue-bound growth factors [ 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. The most abundant proteins of the ECM are collagens [ 17 , 18 ].…”