Mechanisms of Airway Remodeling in Asthma

Abstract

Asthma is a chronic inflammatory disease characterized by reversible airflow limitation and airway hyperresponsiveness. Persistent inflammation in airway tissues may lead to structural changes known as airway remodeling and consequently airway obstruction that is not fully reversible and progressive loss of lung function over time. It is generally accepted that airway remodeling is closely related to progression of airway hyperresponsiveness, and the severity of asthma. The structural changes observed in chronic persistent asthma, which includes airway smooth muscle hypertrophy and hyperplasia, collagen deposition to sub-epithelial basement membrane, hyperplasia of goblet cells, thickening of airway mucosa and an increase in vascularity, are derived from airway inflammation. For instance, the thickened airway mucosa might be produced by cytokines and growth factors released from inflammatory cells and airway epithelial cells, and associated with bronchial hyperreactivity and asthma severity. To date, many studies have identified candidate mechanisms and mediators for these observed structural changes, which are thus potential targets in the treatment of asthma. In this review, we describe the recent knowledge of the mechanisms and clinical implications of airway remodeling in asthma.

HMGB1 contributes to allergen-induced airway remodeling in a murine model of chronic asthma by modulating airway inflammation and activating lung fibroblasts

“…These results demonstrate that HMGB1 promotes the differentiation of fibroblasts into myofibroblasts, which contributes to ECM protein overproduction and deposition in the form of sub-epithelial fibrosis. 29 Consistent with the findings from Hamada et al, 7 50 ng/ml HMGB1 did not affect collagen synthesis; higher concentrations of HMGB1 were required to induce the production of collagen. Moreover, in this study, we did not observe any effects of HMGB1 on the secretion of TGF-b1, MMP-9 or VEGF from MRC-5 cells, strongly suggesting that HMGB1 also exerts a direct profibrotic effect on lung fibroblasts in vitro.…”

Mesenchymal stem cells ameliorate the histopathological changes in a murine model of chronic asthma

“…Airway inflammation in asthma causes subsequent structural changes called as remodeling [15]. The structural changes in asthmatic airways arise as a result of an injury/repair process.…”

17q21 locus and ORMDL3: an increased risk for childhood asthma

“…Airway remodeling in asthma is commonly considered to be a consequence of sustained airway inflammation (60). This assumption has recently been challenged in such that a genetically predisposed asthmatic respiratory tract reacts in a certain way to environmental (allergic or inflammatory) stimuli (61)(62)(63).…”