Airway epithelial cell wound repair mediated by alpha-dystroglycan.
Dystroglycans (DGs) bind laminin matrix proteins in skeletal and cardiac muscle and are expressed in other nonmuscle tissues. However, their expression in airway epithelial cells has not been demonstrated. We examined expression of DGs in the human airway epithelial cell line 1HAEo(-), and in human primary airway epithelial cells. Expression of the common gene for alpha- and beta-DG was demonstrated by reverse transcriptase/ polymerase chain reaction in 1HAEo(-) cells. Protein expression of beta-DG was demonstrated by both Western blot and flow cytometry in cultured cells. Localization of alpha-DG, using both a monoclonal antibody and the alpha-DG binding lectin wheat-germ agglutinin (WGA), was to the cell membrane and nucleus. We then examined the function of DGs in modulating wound repair over laminin matrix. Blocking alpha-DG binding to laminin in 1HAEo(-) monolayers using either glycosyaminoglycans or WGA attenuated cell migration and spreading after mechanical injury. alpha-DG was not expressed in epithelial cells at the wound edge immediately after wound creation, but localized to the cell membrane in these cells within 12 h of injury. These data demonstrate the presence of DGs in airway epithelium. alpha-DG is dynamically expressed and serves as a lectin to bind laminin during airway epithelial cell repair.
White
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SR
Section of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, 5841 S. Maryland Ave., MC6076, Chicago, IL 60637, USA. swhite@medicine.bsd.uchicago.edu
Wojcik
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KR
Gruenert
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D
Sun
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Dorscheid
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DR
D001667:Binding, Competitive; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology; D002465:Cell Movement; D002478:Cells, Cultured / Q000166:cytology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D049030:Dystroglycans; D004847:Epithelial Cells / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008168:Lung / Q000502:physiology; D008175:Lung Neoplasms; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000473:pathology; D016133:Polymerase Chain Reaction; D017474:Receptors, Laminin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014132:Trachea / Q000502:physiology; D014945:Wound Healing / Q000502:physiology*; D014947:Wounds and Injuries
D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D017931:DNA Primers; D007797:Laminin; D008562:Membrane Glycoproteins; D017474:Receptors, Laminin; D049030:Dystroglycans