Airway smooth muscle—its relationship to the extracellular matrix
Section snippets
Multifunctional properties of the airway smooth muscle cell
A new era in airway smooth muscle cell biology began when it was acknowledged that the airway smooth muscle cell did not merely fulfill a structural function, participating in the contraction and relaxation events occurring in the asthmatic airway, but that it had the potential to be an active participant in the inflammatory process which is widely acknowledged to accompany asthma (Hirst, 2003). The muscle mass in the airway wall of individuals with asthma is greatly increased and this is in
Role of the extracellular matrix
Recently it has become important to acknowledge that the muscle is physically associated with a bed of ECM. The ECM consists of a complex network of interlacing macromolecules, which forms a supporting structure for the airway wall. In addition, the ECM has the potential to influence a number of pivotal cellular functions including proliferation, differentiation and migration. The proteins, which constitute the matrix are mainly interstitial collagens, glycoproteins such as fibronectin, laminin
Production and modulation of airway smooth muscle derived matrix proteins
A number of groups have reported that human airway smooth muscle cells in culture can secrete ECM proteins. Panettieri et al. (1998) demonstrated expression of collagens types I and IV, fibronectin, elastin and the chondroitin sulfate proteoglycans biglycan and decorin. TGFβ upregulated expression of collagens I and IV as well as elastin, fibronectin and biglycan. Messenger RNA for decorin, however, was markedly decreased by TGFβ. Johnson et al. (2000) in contrast measured protein release from
Matrix metalloproteinases, their tissue inhibitors and the airway smooth muscle
The MMPs are a large family of enzymes involved in regulation of proteolytic activity and they are a subgroup of a metalloproteinase superfamily which includes ADAM33 (Van Eerdewegh et al., 2002). There are more than 20 MMPs and they share a prodomain and a catalytic domain which contains an active Zn2+ binding site (Parks and Shapiro, 2001). MMPs are secreted as inactive forms, which are activated by proteolytic cleavage of a propeptide sequence capping the catalytic Zn2+ binding domain.
Effects of ECM components on airway smooth muscle properties
It has recently become apparent that, at least in culture, the ECM proteins either secreted by the cells themselves or provided artificially as a coating in culture plates or wells can profoundly influence smooth muscle cell behavior. Hirst et al. (2000) examined the proliferative response of airway smooth muscle cells to mitogens after they had been seeded onto a matrix of variable composition. Whereas fibronectin and collagen I increased the proliferative response, laminin caused a reduction.
Potential for functional consequences
In asthma there are both quantitative and qualitative abnormalities in the ECM. These can be localized external to the airway smooth muscle, within the muscle bundles (Bai et al., 2000) or between the muscle and the epithelial layer. Increased matrix deposition external to the smooth muscle may decrease airway-parenchymal interdependence and this may result in exaggerated airway narrowing (Macklem, 1995). The effects of collagen deposition are most likely to depend on the architecture of the
Acknowledgements
The authors are supported by the NH&MRC Australia, Glaxo Smith Kline UK and AstraZeneca, Sweden.
References (39)
- et al.
Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3
Cell
(1996) - et al.
Increased MMP-2 expression in connective tissue growth factor over-expression vascular smooth muscle cells
J. Biol. Chem.
(2002) - et al.
The cytoskeleton and the extracellular matrix in sensitized canine tracheal smooth muscle
Respir. Physiol.
(1997) Theoretical basis of airway instability. Roger S. Mitchell lecture
Chest
(1995)Is asthma a fibrotic disease
Chest
(1995)- et al.
Local overexpression of TIMP-1 prevents aortic aneurysm degeneration and rupture in a rat model
J. Clin. Invest.
(1998) - et al.
Structure and biological activity of the extracellular matrix
J. Mol. Med.
(1998) - et al.
The effect of age and duration of disease on airway structure in fatal asthma
Am. J. Respir. Crit. Care Med.
(2000) - et al.
Divergent effects of tissue inhibitor of metalloproteinase-1, -2, or -3 overexpression on rat vascular smooth muscle cell invasion, proliferation, and death in vitro. TIMP-3 promotes apoptosis
J. Clin. Invest.
(1998) - et al.
Expression of betaig-h3 by human bronchial smooth muscle cells: localization to the extracellular matrix and nucleus
Am. J. Respir. Cell Mol. Biol.
(2000)
Asthma: a disease remodeling the airways
Allergy
Airways remodelling in asthma: no doubt, no more
Int. Arch. Allergy Immunol.
Collagenase increases shortening of human bronchial smooth muscle in vitro
Am. J. Respir. Crit. Care Med.
Release of biologically active TGF-beta from airway smooth muscle cells induces autocrine synthesis of collagen
Am. J. Physiol. Lung Cell. Mol. Physiol.
Cellular hypertrophy and hyperplasia of airway smooth muscles underlying bronchial asthma. A 3-D morphometric study
Am. Rev. Respir. Dis.
Effects of growth factors and extracellular matrix on survival of human airway smooth muscle cells
Am. J. Respir. Cell Mol. Biol.
Airway smooth muscle cell culture: application to studies of airway wall remodelling and phenotype plasticity in asthma
Eur. Respir. J.
Airway smooth muscle as a target in asthma
Clin. Exp. Allergy
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