title: Shear stress regulates aquaporin-5 and airway epithelial barrier function.
abstract: As the interface with the outside world, the airway epithelial barrier is critical to lung defense. Because of respiratory efforts, the airways are exposed to shear stress; however, little is known regarding the effects of shear on epithelial function. We report that low-level shear stress enhances epithelial barrier function, an effect that requires serial activation of the transient receptor potential vanilloid (TRPV) 4 and L-type voltage-gated calcium channel (VGCC) and an increase in intracellular calcium. These changes lead to a selective decrease in aquaporin-5 (AQP5) abundance because of protein internalization and degradation. To determine whether AQP5 plays a role in mediating the shear effects on paracellular permeability, we overexpressed hAQP5 in 16HBE cells, an airway epithelial cell line without endogenous AQP5. We found that AQP5 expression was needed for shear-induced barrier enhancement. These findings have direct relevance to the regulation of epithelial barrier function, membrane permeability, and water homeostasis in the respiratory epithelia.
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Venkataramana K
authors.initials: VK
authors.lastname: Sidhaye
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Schweitzer
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Caterina
authors.forename: Larissa
authors.initials: L
authors.lastname: Shimoda
authors.forename: Landon S
authors.initials: LS
authors.lastname: King
mesh_terms: D000818:Animals; D051402:Aquaporin 5 / Q000502:physiology*; D001692:Biological Transport; D002118:Calcium; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002463:Cell Membrane Permeability; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D020545:Respiratory Mucosa / Q000502:physiology*; D013314:Stress, Mechanical; D050916:TRPV Cation Channels / Q000378:metabolism*; D014867:Water
chemical_list: D051402:Aquaporin 5; D020746:Calcium Channels, L-Type; D050916:TRPV Cation Channels; C416986:TRPV4 protein, human; D014867:Water; D002118:Calcium