Fibroblast-to-myofibroblast transition in bronchial asthma

Abstract

Bronchial asthma is a chronic inflammatory disease in which bronchial wall remodelling plays a significant role. This phenomenon is related to enhanced proliferation of airway smooth muscle cells, elevated extracellular matrix protein secretion and an increased number of myofibroblasts. Phenotypic fibroblast-to-myofibroblast transition represents one of the primary mechanisms by which myofibroblasts arise in fibrotic lung tissue. Fibroblast-to-myofibroblast transition requires a combination of several types of factors, the most important of which are divided into humoural and mechanical factors, as well as certain extracellular matrix proteins. Despite intensive research on the nature of this process, its underlying mechanisms during bronchial airway wall remodelling in asthma are not yet fully clarified. This review focuses on what is known about the nature of fibroblast-to-myofibroblast transition in asthma. We aim to consider possible mechanisms and conditions that may play an important role in fibroblast-to-myofibroblast transition but have not yet been discussed in this context. Recent studies have shown that some inherent and previously undescribed features of fibroblasts can also play a significant role in fibroblast-to-myofibroblast transition. Differences observed between asthmatic and non-asthmatic bronchial fibroblasts (e.g., response to transforming growth factor β, cell shape, elasticity, and protein expression profile) may have a crucial influence on this phenomenon. An accurate understanding and recognition of all factors affecting fibroblast-to-myofibroblast transition might provide an opportunity to discover efficient methods of counteracting this phenomenon.

Responsiveness of human bronchial fibroblasts and epithelial cells from asthmatic and non-asthmatic donors to the transforming growth factor-β1 in epithelial-mesenchymal trophic unit model

“…It suggests that not only SNAI1/SNAI2 ratio is involved in the EMT by modulation of HBECs responsiveness to the TGF-β1, but also the intrinsic properties of HBFs may have a protective effect on the HBECs reactivity. Despite that, our hypothesis requires further research to show which features of HBFs may have a significant effect on the EMT potential of bronchial HBECs cultured in the EMTU, which is in accordance with our previous reports about different features associated with the FMT potential of the AS HBFs in comparison to the NA ones observed in both standard '2D' conditions [20] and the non-treated AS/AS or NA/NA EMTU presented in our study for the first time. These…”

“…Different properties of the normal and asthmatic HBFs as well as the bronchial epithelium cultured independently in vitro were described previously [20,29,30]. In this study, we checked the properties and sensitivity to the TGF-β1 of these cells from asthmatics and non-asthmatics growing in co-cultures AS/AS and NA/NA in in vitro EMTU model ( Fig.…”

“…Longitudinal studies reveal that the subepithelial layer containing airway fibroblasts is also effectively activated by profibrotic cytokines, including the TGF-β1, to phenotypic shifts into highly contractile myofibroblasts (fibroblast-to-myofibroblast transition, FMT). These cells are characterized by overexpression of α-smooth muscle actin (α-SMA) incorporated into microfilament bundles, and hypersecretion of the extracellular matrix (ECM) proteins as tenascin C, collagens and fibronectin [20]. The excessive secretory activity of myofibroblasts leads to thickening of the subepithelial layer which effectively impairs the respiratory tract functions with its enhanced contractility [8].…”

LncRNA ANRIL/miR‐125a axis exhibits potential as a biomarker for disease exacerbation, severity, and inflammation in bronchial asthma

“…Many asthma patients are relieved by treatment with β2‐adrenergic receptor antagonist and inhaled corticosteroids or a leukotriene receptor antagonist, and however, the traditional anti‐inflammatory drugs have defects associated with high‐dose side effects, and novel therapeutic approaches such as antigen specific therapy and cytokine‐specific antagonists still require further improvement in safety and efficacy . Moreover, there are still a large number of patients who succumb to more severe disease with more frequent symptoms and exacerbations . Therefore, exploring additional molecular targets would be of great benefit for general asthma patients including those with disease exacerbation.…”

“…3,4 Moreover, there are still a large number of patients who succumb to more severe disease with more frequent symptoms and exacerbations. 5 Therefore, exploring additional molecular targets would be of great benefit for general asthma patients including those with disease exacerbation.…”