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Review
. 2017 Aug 16;18(1):156.
doi: 10.1186/s12931-017-0640-8.

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

Brittany Salter  1 , Cara Pray  1 , Katherine Radford  1 , James G Martin  2 , Parameswaran Nair  3
Affiliations
Review

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

Brittany Salter et al. Respir Res. .

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.

Keywords: Airway smooth muscle; Asthma; Cytokines; Migration; Remodelling.

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Figures

Fig. 1
Fig. 1
a: The process of ASMC migration can be divided into 5 steps: cell polarization, protrustion, adhesion, contraction, and retraction. These steps are controlled by specific signaling proteins, which are modulated by external stimuli. The signaling proteins are described in Fig. 1A. b: Cell migration is initiated by activation of receptors such as G protein-coupled receptors (GPCRs), receptor tyrosine kinases (RTK), and integrins, which trigger downstream intracellular signaling, resulting in airway smooth muscle cell (ASMC) migration. An important contributing factor to ASMC migration is actin polymerization, which is a proximal event that propels the leading cell edge towards external stimuli. Various mediators and the extracellular matrix (ECM), for example PDGF, HB-EGF, TGF-β, can activate these membrane receptors. Post-receptor activation, there is downstream induction of trimeric G proteins, Src tyrsoine kinases, phospholipase C, PIP2, c-Abl, and PI3K. This is followed by subsequent activation of signaling proteins (Cdc42, Ras, Rac, Rho, Cortactin, FAK, Akt, PKA, etc), which regulate cell polarization, actin polymerization and traction force. There are various downstream targets that are integral to these processes including the effector proteins mDIA1, WAVE, WASP, ARP2/3 complex. Additional downstream regulators include members of the MAPK family p38 MAPK, ERK, Rho kinase (ROCK), and p21-activated protein kinases (PAK). This results in further phosphorylation of other protein kinases including MAPKAPK, LIMK or phosphatases like MLCP, which then regulate effector proteins that control actin polymerization (HSP20, HSP27, Cortactin, Pin-1, Cofilin) and traction forces (myosin II). Actin polymerization is controlled via complex processes that involve actin branching, actin elongation, and de-branching. This figure is a simplified illustration of the various signaling pathways, which is in reality far more complex then this. These processes are thoroughly reviewed by Tang [127] and Gerthoffer et al. [128]. Red arrows indicate inhibition, green arrows indicate stimulation. Purple circles indicate the most upstream signaling proteins, lightest blue circles indicate effector proteins, including small G proteins, and darker blue circles represent proteins that directly regulate ASMC migration
Fig. 2
Fig. 2
Airway remodeling is an important feature of asthma pathogenesis. An important contribution to airway remodeling is increased ASM mass, which is thought to be brought on by ASMC migration, thereby adding to the local cellular hyperplasia. The source of these ASMCs has been thought to be due to local infiltration of myfibroblasts, neighbouring ASMCs, and circulating HPCs. Various mediators have been identified that influence ASMC migration, which are outlined in this figure. Local pro-inflammatory mediators produced by airway epithelial cells, including TGF-β, PDGF, EGF, PGD2, CXCL2, CXCL3, IL-8, eotaxin, TSLP, and CCL19 have been shown to induce ASMC migration, whereas PGE2 and Lipoxin A2 inhibit ASMC migration. In addition, inflammatory cytokines produced by Th17 and Th2 cells, as well as CysLTs produced by basophils and mast cells, further contribute to ASMC migration. Conversely, systemically circulating leptin inhibits ASMC migration. Abbreviations: EP- epithelium; LP- lamina propria; ASM- Airway Smooth Muscle; ASMCs- Airway Smooth Muscle Cells; HPCs- hemopoetic progenitor cells; CysLTs- cysteinyl leukotrienes
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References

    1. Huber HL, Koessler KK. The pathology of bronchial asthma. Arch Intern Med. 1922;30:689–760. doi: 10.1001/archinte.1922.00110120002001. - DOI
    1. Dunhill MS, Massarella GR, Anderson JA. A comparison of the quantitative anatomy of the bronchi in normal subjects, in status asthmaticus, in chronic bronchitis and in emphysema. Thorax. 1971;24:176–179. doi: 10.1136/thx.24.2.176. - DOI - PMC - PubMed
    1. Takizawa T, Thurlbeck WM. Muscle and mucous gland size in the major bronchi of patients with chronic bronchitis, asthma and asthmatic bronchitis. Am Rev Respir Dis. 1971;104:331–336. doi: 10.1164/arrd.1971.104.3.331. - DOI - PubMed
    1. Heard BE, Hossain S. Hyperplasia of bronchial smooth muscle in asthma. J Pathol. 1973;110:319–312. doi: 10.1002/path.1711100406. - DOI
    1. Sobonya RE. Quantitative structural alterations in long-standing allergic asthma. Am Rev Respir Dis. 1984;130:289–292. - PubMed

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