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-β 1 ) 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 μg/ml with 1 μg/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-β 1 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. airway remodeling extracellular matrix chronic obstructive pulmonary disease asthma transforming growth factor-β Copyright © 2012 the American Physiological Society « Previous | Next Article » Table of Contents This Article Published online before print October 2011 , doi: 10.​1152/​ajplung.​00453.​2010 AJP - Lung Physiol February 2012 vol. 302 no. 3 L325-L333 » Abstract Free Full Text Free to you Full Text (PDF) Free to you All Versions of this Article: ajplung.00453.2010v1 302/3/L325 most recent Classifications Article Services Email this article to a friend Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Citing articles via Web of Science Google Scholar Articles by Ichimaru, Y. Articles by Oliver, B. G. G. PubMed PubMed citation Articles by Ichimaru, Y. Articles by Oliver, B. G. G. Related Content Load related web page information Current Issue February 2012, 302 (3) Alert me to new issues of AJP - Lung Physiol About the Journal Information for Authors Submit a Manuscript Ethical Policies AuthorChoice PubMed Central Policy Reprints and Permissions Advertising Press Copyright © 2012 the American Physiological Society Print ISSN: 1040-0605 Online ISSN: 1522-1504 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); var pageTracker = _gat._getTracker("UA-2924550-1"); pageTracker._trackPageview();

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