title: The effect of hyaluronan on airway mucus transport and airway epithelial barrier integrity: potential application to the cytoprotection of airway tissue.
abstract: The lubricating abilities and the protective functions of hyaluronan, a structural component of interstitial and connective tissues, were assessed in in vitro models of airway mucus transport and epithelial barrier. We found that hyaluronan enhanced the transport of airway mucus by cilia and by cough: the lower the hyaluronan molecular weight, the higher the increase. By immunofluorescence and western blot, we observed a significant dose-dependent (0.1, 1, 5 and 10 mg/ml) increase by low molecular weight hyaluronan (40 kDa) in the expression of tight junction proteins such as ZO-1, as well as an increase in the trans-epithelial resistance. Incubation of airway epithelial cells with hyaluronan 40 kDa also significantly increased the gap junction functionality. Finally, we demonstrated that hyaluronan 40 kDa protects the airway epithelium against injury induced by bacterial products during infection. These results demonstrate that the expression and functionality of intercellular adhesion molecules are increased by hyaluronan which can also act as a lubricant at the airway epithelium surface and suggest that hyaluronan may play a therapeutic role in a variety of respiratory diseases.
authors.affiliation: INSERM, U903, Reims, F-51092, France. jm.zahm@univ-reims.fr
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Zahm
authors.forename: Magali
authors.initials: M
authors.lastname: Milliot
authors.forename: Anthony
authors.initials: A
authors.lastname: Bresin
authors.forename: Christelle
authors.initials: C
authors.lastname: Coraux
authors.forename: Philippe
authors.initials: P
authors.lastname: Birembaut
mesh_terms: D001692:Biological Transport; D015153:Blotting, Western; D016923:Cell Death; D002460:Cell Line; D002923:Cilia / Q000378:metabolism / Q000502:physiology; D003371:Cough / Q000188:drug therapy / Q000503:physiopathology*; D019610:Cytoprotection; D005285:Fermentation; D005455:Fluorescent Antibody Technique; D017629:Gap Junctions / Q000378:metabolism / Q000502:physiology; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D008970:Molecular Weight; D009093:Mucus / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology / Q000502:physiology; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D018502:Streptococcus equi / Q000737:chemistry; D013499:Surface Properties; D019108:Tight Junctions / Q000378:metabolism / Q000502:physiology; D062826:Zonula Occludens-1 Protein
chemical_list: D008565:Membrane Proteins; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D006820:Hyaluronic Acid