Expression of the dystrophin-glycoprotein complex is a marker for human airway smooth muscle phenotype maturation
| Autor: | Andrew J. Halayko, Mark M. Mutawe, Gerald L. Stelmack, Karol D. McNeill, Reinoud Gosens, William T. Gerthoffer, Pawan K. Sharma, Thai Tran, Helmut Unruh |
|---|---|
| Přispěvatelé: | Molecular Pharmacology, Groningen Research Institute for Asthma and COPD (GRIAC) |
| Rok vydání: | 2008 |
| Předmět: |
Genetic Markers
Pulmonary and Respiratory Medicine Physiology Calponin Cell Line Dystrophin Wortmannin chemistry.chemical_compound Laminin Sarcoglycans Physiology (medical) medicine Humans Dystroglycans Telomerase Cellular Senescence Glycoproteins Smooth muscle tissue Sarcolemma biology Reverse Transcriptase Polymerase Chain Reaction Muscle Smooth Cell Biology musculoskeletal system Actin cytoskeleton Immunohistochemistry Cell biology Protein Subunits Phenotype medicine.anatomical_structure Biochemistry chemistry Cell Aging Respiratory Physiological Phenomena biology.protein Muscle Smooth Cell aging |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology, 294(1), L57-L68. AMER PHYSIOLOGICAL SOC |
| ISSN: | 1522-1504 1040-0605 |
| Popis: | 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 beta-dystroglycan, beta-, delta-, and epsilon-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 microM) and phosphatidylinositol 3-kinase (PI3K) inhibitors (20 microM 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|