Transforming growth factor beta 1 increases fibronectin deposition through integrin receptor alpha 5 beta 1 on human airway smooth muscle.
BACKGROUND
Integrin receptors signal to and from the extracellular matrix. Altered expression of the integrin receptors, such as the fibronectin receptor alpha(5)beta(1), might be implicated in extracellular matrix accumulation in airway remodeling in asthma.


OBJECTIVE
We examined the effect of TGF-beta stimulation on integrin alpha(5)beta(1) expression and the role of alpha(5)beta(1) in fibronectin deposition and proliferation.


METHODS
Integrin subunit alpha(5) and beta(1) expression in airway smooth muscle (ASM) from subjects with and without asthma was examined by means of PCR and flow cytometry. The effect of blocking alpha(5)beta(1) receptor on ASM proliferation to FBS was assessed by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium assay. Cells were stimulated with TGF-beta in the presence or absence of extracellular signal-regulated kinase, phosphoinositide-3 kinase, or p38 inhibitors and antibodies to the alpha(5) and beta(1) subunits. The effect of blocking alpha(5)beta(1) receptor on fibronectin deposition was assessed by means of immunocytochemistry.


RESULTS
Proliferation of ASM cells from asthmatic and nonasthmatic subjects was inhibited by blocking the fibronectin receptor subunit alpha(5)beta(1). TGF-beta-induced alpha(5)beta(1) was extracellular signal-regulated kinase dependent but not phosphoinositide-3 kinase or p38 dependent. Blockade of the alpha(5)beta(1) receptor inhibited TGF-beta-induced fibronectin matrix deposition.


CONCLUSIONS
Through its increased expression by the profibrotic stimulus TGF-beta, integrin alpha(5)beta(1) might be important in regulating fibronectin deposition.
Moir
Lyn M
LM
Woolcock Institute of Medical Research, University of Sydney, Sydney, Australia. lynmoir@med.usyd.edu.au
Burgess
Janette K
JK
Black
Judith L
JL
D000328:Adult; D001249:Asthma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D001980:Bronchi / Q000166:cytology / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D039081:Integrin alpha5beta1 / Q000096:biosynthesis / Q000502:physiology*; D008168:Lung / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000276:immunology; D008875:Middle Aged; D009130:Muscle, Smooth / Q000276:immunology* / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000502:physiology*; D015854:Up-Regulation / Q000276:immunology*
D005353:Fibronectins; D039081:Integrin alpha5beta1; D053773:Transforming Growth Factor beta1; D048049:Extracellular Signal-Regulated MAP Kinases