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This Article Full Text Full Text (PDF) All Versions of this Article: 294/1/L57    most recent 00378.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Sharma, P. Articles by Halayko, A. J. Search for Related Content PubMed PubMed Citation Articles by Sharma, P. Articles by Halayko, A. J.

Expression of the dystrophin-glycoprotein complex is a marker for human airway smooth muscle phenotype maturation

Departments of ¹Physiology, ²Internal Medicine, and ³Pediatrics and Child Health, ⁴Section of Respiratory Disease, ⁵Section of Thoracic Surgery, and ⁶Canadian Institute of Health Research National Training Program in Allergy and Asthma, University of Manitoba and ⁷Biology of Breathing Group, Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada; and ⁸Department of Pharmacology, University of Nevada School of Medicine, Reno, Nevada

Submitted 12 September 2007 ; accepted in final form 3 November 2007

Airway smooth muscle (ASM) cells may contribute to asthma pathogenesis through their capacity to switch between a synthetic/proliferative and a contractile phenotype. The multimeric dystrophin-glycoprotein complex (DGC) spans the sarcolemma, linking the actin cytoskeleton and extracellular matrix. The DGC is expressed in smooth muscle tissue, but its functional role is not fully established. We tested whether contractile phenotype maturation of human ASM is associated with accumulation of DGC proteins. We compared subconfluent, serum-fed cultures and confluent cultures subjected to serum deprivation, which express a contractile phenotype. Western blotting confirmed that β-dystroglycan, β-, -, and -sarcoglycan, and dystrophin abundance increased six- to eightfold in association with smooth muscle myosin heavy chain (smMHC) and calponin accumulation during 4-day serum deprivation. Immunocytochemistry showed that the accumulation of DGC subunits was specifically localized to a subset of cells that exhibit robust staining for smMHC. Laminin competing peptide (YIGSR, 1 µM) and phosphatidylinositol 3-kinase (PI3K) inhibitors (20 µM LY-294002 or 100 nM wortmannin) abrogated the accumulation of smMHC, calponin, and DGC proteins. These studies demonstrate that the accumulation of DGC is an integral feature for phenotype maturation of human ASM cells. This provides a strong rationale for future studies investigating the role of the DGC in ASM smooth muscle physiology in health and disease.

sarcoglycans; phosphatidylinositol 3-kinase; laminin; differentiation