Transforming growth factor β1 increases fibronectin deposition through integrin receptor ⍺5β1 on human airway smooth muscle - 15/08/11
, Janette K. Burgess, PhD a, b, Judith L. Black, MBBS, PhD a, b
Reprint requests: Lyn M. Moir, PhD, Discipline of Pharmacology, Bosch Building D05, University of Sydney, Sydney, NSW, 2006, Australia.Abstract |
Background |
Integrin receptors signal to and from the extracellular matrix. Altered expression of the integrin receptors, such as the fibronectin receptor ⍺5β1, might be implicated in extracellular matrix accumulation in airway remodeling in asthma.
Objective |
We examined the effect of TGF-β stimulation on integrin ⍺5β1 expression and the role of ⍺5β1 in fibronectin deposition and proliferation.
Methods |
Integrin subunit ⍺5 and β1 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 ⍺5β1 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-β in the presence or absence of extracellular signal-regulated kinase, phosphoinositide-3 kinase, or p38 inhibitors and antibodies to the ⍺5 and β1 subunits. The effect of blocking ⍺5β1 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 ⍺5β1. TGF-β–induced ⍺5β1 was extracellular signal-regulated kinase dependent but not phosphoinositide-3 kinase or p38 dependent. Blockade of the ⍺5β1 receptor inhibited TGF-β–induced fibronectin matrix deposition.
Conclusion |
Through its increased expression by the profibrotic stimulus TGF-β, integrin ⍺5β1 might be important in regulating fibronectin deposition.
Le texte complet de cet article est disponible en PDF.Key words : Human airway smooth muscle, integrins, transforming growth factor β, proliferation, fibronectin, fibrosis, extracellular matrix
Abbreviations used : ASM, CT, DMEM, ECM, ERK, fb-mAb, ITS, PI3K
Plan
| Supported by the National Health and Medical Research Council, Australia. J. K. Burgess is supported by National Health and Medical Research Council R. Douglas Wright Fellowship no. 402835. |
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| Disclosure of potential conflict of interest: The authors have declared that they have no relevant conflict of interest. |
Vol 121 - N° 4
P. 1034 - avril 2008 Retour au numéro
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