TGF-β enhances deposition of perlecan from COPD airway smooth muscle

Ichimaru, Y; Krimmer, DI; Burgess, JK; Black, JL; Oliver, BGG

TGF-β enhances deposition of perlecan from COPD airway smooth muscle

Ichimaru, Y Krimmer, DI Burgess, JK Black, JL Oliver, BGG

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Publication Type:: Journal Article
Citation:: American Journal of Physiology - Lung Cellular and Molecular Physiology, 2012, 302 (3)
Issue Date:: 2012-02-01

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Field	Value	Language
dc.contributor.author	Ichimaru, Y	en_US
dc.contributor.author	Krimmer, DI	en_US
dc.contributor.author	Burgess, JK	en_US
dc.contributor.author	Black, JL	en_US
dc.contributor.author	Oliver, BGG https://orcid.org/0000-0002-7122-9262	en_US
dc.date.issued	2012-02-01	en_US
dc.identifier.citation	American Journal of Physiology - Lung Cellular and Molecular Physiology, 2012, 302 (3)	en_US
dc.identifier.issn	1040-0605	en_US
dc.identifier.uri	http://hdl.handle.net/10453/29761
dc.description.abstract	Chronic obstructive pulmonary disease (COPD) and asthma are characterized by irreversible remodeling of the airway walls, including thickening of the airway smooth muscle layer. Perlecan is a large, multidomain, proteoglycan that is expressed in the lungs, and in other organ systems, and has been described to have a role in cell adhesion, angiogenesis, and proliferation. This study aimed to investigate functional properties of the different perlecan domains in relation to airway smooth muscle cells (ASMC). Primary human ASMC obtained from donors with asthma (n = 13), COPD (n = 12), or other lung disease (n = 20) were stimulated in vitro with 1 ng/ml transforming growth factor- β 1 (TGF-(31) before perlecan deposition and cytokine release were analyzed. In some experiments, inhibitors of signaling molecules were added. Perlecan domains I-V were seeded on tissue culture plates at 10 (xg/ml with 1 (xg/ml collagen I as a control. ASM was incubated on top of the peptides before being analyzed for attachment, proliferation, and wound healing. TGF-β 1 upregulated deposition of perlecan by ASMC from COPD subjects only. TGF-(31 upregulated release of IL-6 into the supernatant of ASMC from all subjects. Inhibitors of SMAD and JNK signaling molecules decreased TGF-β 1-induced perlecan deposition by COPD ASMC. Attachment of COPD ASMC was upregulated by collagen I and perlecan domains IV and V, while perlecan domain II upregulated attachment only of asthmatic ASMC. Seeding on perlecan domains did not increase proliferation of any ASMC type. TGF-β 1-induced perlecan deposition may enhance attachment of migrating ASMC in vivo and thus may be a mechanism for ASMC layer hypertrophy in COPD. © 2012 the American Physiological Society.	en_US
dc.relation.ispartof	American Journal of Physiology - Lung Cellular and Molecular Physiology	en_US
dc.relation.isbasedon	10.1152/ajplung.00453.2010	en_US
dc.subject.classification	Respiratory System	en_US
dc.subject.mesh	Muscle, Smooth	en_US
dc.subject.mesh	Cells, Cultured	en_US
dc.subject.mesh	Extracellular Matrix	en_US
dc.subject.mesh	Myocytes, Smooth Muscle	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Lung Neoplasms	en_US
dc.subject.mesh	Asthma	en_US
dc.subject.mesh	Pulmonary Disease, Chronic Obstructive	en_US
dc.subject.mesh	MAP Kinase Kinase 4	en_US
dc.subject.mesh	Cell Adhesion	en_US
dc.subject.mesh	Cell Proliferation	en_US
dc.subject.mesh	Cell Movement	en_US
dc.subject.mesh	MAP Kinase Signaling System	en_US
dc.subject.mesh	Protein Structure, Tertiary	en_US
dc.subject.mesh	Phosphorylation	en_US
dc.subject.mesh	Adult	en_US
dc.subject.mesh	Aged	en_US
dc.subject.mesh	Middle Aged	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Smad Proteins	en_US
dc.subject.mesh	Transforming Growth Factor beta1	en_US
dc.subject.mesh	Heparan Sulfate Proteoglycans	en_US
dc.subject.mesh	Immobilized Proteins	en_US
dc.subject.mesh	Young Adult	en_US
dc.title	TGF-β enhances deposition of perlecan from COPD airway smooth muscle	en_US
dc.type	Journal Article
utslib.citation.volume	3	en_US
utslib.citation.volume	302	en_US
utslib.for	0606 Physiology	en_US
utslib.for	1116 Medical Physiology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	closed_access
pubs.issue	3	en_US
pubs.publication-status	Published	en_US
pubs.volume	302	en_US

Abstract:

Chronic obstructive pulmonary disease (COPD) and asthma are characterized by irreversible remodeling of the airway walls, including thickening of the airway smooth muscle layer. Perlecan is a large, multidomain, proteoglycan that is expressed in the lungs, and in other organ systems, and has been described to have a role in cell adhesion, angiogenesis, and proliferation. This study aimed to investigate functional properties of the different perlecan domains in relation to airway smooth muscle cells (ASMC). Primary human ASMC obtained from donors with asthma (n = 13), COPD (n = 12), or other lung disease (n = 20) were stimulated in vitro with 1 ng/ml transforming growth factor- β 1 (TGF-(31) before perlecan deposition and cytokine release were analyzed. In some experiments, inhibitors of signaling molecules were added. Perlecan domains I-V were seeded on tissue culture plates at 10 (xg/ml with 1 (xg/ml collagen I as a control. ASM was incubated on top of the peptides before being analyzed for attachment, proliferation, and wound healing. TGF-β 1 upregulated deposition of perlecan by ASMC from COPD subjects only. TGF-(31 upregulated release of IL-6 into the supernatant of ASMC from all subjects. Inhibitors of SMAD and JNK signaling molecules decreased TGF-β 1-induced perlecan deposition by COPD ASMC. Attachment of COPD ASMC was upregulated by collagen I and perlecan domains IV and V, while perlecan domain II upregulated attachment only of asthmatic ASMC. Seeding on perlecan domains did not increase proliferation of any ASMC type. TGF-β 1-induced perlecan deposition may enhance attachment of migrating ASMC in vivo and thus may be a mechanism for ASMC layer hypertrophy in COPD. © 2012 the American Physiological Society.

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http://hdl.handle.net/10453/29761