Regulation of human airway smooth muscle cell migration and relevance to asthma

Abstract

Airway remodelling is an important feature of asthma pathogenesis. A key structural change inherent in airway remodelling is increased airway smooth muscle mass. There is emerging evidence to suggest that the migration of airway smooth muscle cells may contribute to cellular hyperplasia, and thus increased airway smooth muscle mass. The precise source of these cells remains unknown. Increased airway smooth muscle mass may be collectively due to airway infiltration of myofibroblasts, neighbouring airway smooth muscle cells in the bundle, or circulating hemopoietic progenitor cells. However, the relative contribution of each cell type is not well understood. In addition, although many studies have identified pro and anti-migratory agents of airway smooth muscle cells, whether these agents can impact airway remodelling in the context of human asthma, remains to be elucidated. As such, further research is required to determine the exact mechanism behind airway smooth muscle cell migration within the airways, how much this contributes to airway smooth muscle mass in asthma, and whether attenuating this migration may provide a therapeutic avenue for asthma. In this review article, we will discuss the current evidence with respect to the regulation of airway smooth muscle cell migration in asthma.

Fibroblast-to-myofibroblast transition in bronchial asthma

“…Many reports have also shown that myofibroblasts are an abundant source of inflammatory mediators, cytokines, chemokines, and growth factors, such as granulocyte–macrophage colony-stimulating factor (GM-CSF), interleukins (IL-1, IL-6, IL-8), stem cell factor (SCF), transforming growth factor type β (TGF-β), and vascular endothelial growth factor (VEGF) [ 63 – 66 ]. Thus, myofibroblast-derived factors may act not only on themselves but also on other airway and immune cells, such as smooth muscle cells, by promoting cell migration, hyperplasia and hypertrophy [ 67 , 68 ].…”

Biological Therapies of Severe Asthma and Their Possible Effects on Airway Remodeling

“…Thus, AR is a change of composition, content and distribution of cellular and molecular components in the airway wall (19). In asthma, it is associated with many structural changes-epithelial damage, subepithelial fibrosis, angiogenesis, hypertrophy and proliferation of myofibroblasts and myocytes and increased number of smooth muscle fibers in airway smooth muscle cells (ASMC), that increase airway smooth muscle (ASM) mass (20,21). A number of inflammatory molecular factors are involved in these structural changes, either directly or via further induction of inflammatory reaction, namely eosinophilic (22).…”

RNase 2/EDN cleaves the anticodon loops of tRNAs to produce immunostimulatory tRNA halves in asthma

“…ASM cells located in the smooth muscle layer undergo phenotypic modification attaining hyperproliferative phenotype. In addition, studies have shown that ASM cells are capable of migration in response to chemotactic factors released during inflammation or arising from the injured epithelium [58][59][60], and this migration may contribute to cellular hyperplasia [58]. It is possible that myofibroblasts, which have been observed around the airways in the asthmatics, could be smooth muscle cells that have migrated luminally.…”