Tissue and matrix influences on airway smooth muscle function.
Asthma is characterized by structural changes in the airways - airway remodelling. These changes include an increase in the bulk of the airway smooth muscle (ASM) and alterations in the profile of extracellular matrix (ECM) proteins in the airway wall. The mechanisms leading to airway remodelling are not well understood. ASM cells have the potential to play a key role in these processes through the production and release of ECM proteins. The ASM cells and ECM proteins are each able to influence the behaviour and characteristics of the other. The modified ECM profile in the asthmatic airway may contribute to the altered behaviour of the ASM cells, such responses to ECM proteins are modulated through the cell surface expression of integrin receptors. ASM cells from asthmatic individuals express different levels of some integrin subunits compared to nonasthmatic ASM cells, which have the potential to further influence their responses to the ECM proteins in the airways. ECM homeostasis requires the presence and activation of matrix metalloproteinases and their tissue inhibitors, which in turn modulate the interaction of the ASM cells and the ECM proteins. Furthermore, the complex interactions of the ASM cells and the ECM in the asthmatic airways and the role played by external stimuli, such as viral infections, to modulate airway remodelling are currently unknown. This review summarises our current understanding of the influence of the ECM on ASM function.
Burgess
Janette K
JK
Discipline of Pharmacology, Bosch Institute, University of Sydney, Sydney, Australia. janette@pharmacol.usyd.edu.au
Ceresa
Claudia
C
Johnson
Simon R
SR
Kanabar
Varsha
V
Moir
Lyn M
LM
Nguyen
Trang T B
TT
Oliver
Brian G G
BG
Schuliga
Michael
M
Ward
Jane
J
D001249:Asthma / Q000378:metabolism / Q000473:pathology*; D001980:Bronchi / Q000502:physiology*; D016535:Bronchial Hyperreactivity / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008954:Models, Biological; D032342:Muscle Cells / Q000378:metabolism / Q000473:pathology; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology*; D011024:Pneumonia, Viral / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000378:metabolism; D012137:Respiratory System / Q000378:metabolism / Q000473:pathology*
D016326:Extracellular Matrix Proteins; D016023:Integrins; D020782:Matrix Metalloproteinases