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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.

SUBMITTER: Sidhaye VK

PROVIDER: S-EPMC2265191 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature

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Shear stress regulates aquaporin-5 and airway epithelial barrier function.

Sidhaye Venkataramana K VK Schweitzer Kelly S KS Caterina Michael J MJ Shimoda Larissa L King Landon S LS

Proceedings of the National Academy of Sciences of the United States of America 20080227 9

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 intrace ...[more]

PMID: 18305162

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Project description:BackgroundThe airway epithelial barrier function is disrupted in the airways of asthmatic patients. Abnormal mitochondrial biogenesis is reportedly involved in the pathogenesis of asthma. However, the role of mitochondrial biogenesis in the airway barrier dysfunction has not been elucidated yet. This study aimed to clarify whether the peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α), a central regulator of mitochondrial biogenesis, is involved in the disruption of the airway barrier function induced by aeroallergens.MethodsBEAS-2B cells were exposed to house dust mite (HDM) and the expressions of PGC-1α and E-cadherin, a junctional protein, were examined by immunoblotting. The effect of SRT1720, a PGC-1α activator, was investigated by immunoblotting, immunocytochemistry, and measuring the transepithelial electrical resistance (TEER) on the HDM-induced reduction in mitochondrial biogenesis markers and junctional proteins in airway bronchial epithelial cells. Furthermore,the effects of protease activated receptor 2 (PAR2) inhibitor, GB83, Toll-like receptor 4 (TLR4) inhibitor, lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS), protease inhibitors including E64 and 4-(2-Aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) on the HDM-induced barrier dysfunction were investigated.ResultsThe amounts of PGC-1α and E-cadherin in the HDM-treated cells were significantly decreased compared to the vehicle-treated cells. SRT1720 restored the expressions of PGC-1α and E-cadherin reduced by HDM in BEAS-2B cells. Treatment with SRT1720 also significantly ameliorated the HDM-induced reduction in TEER. In addition, GB83, LPS-RS, E64 and AEBSF prevented the HDM-induced reduction in the expression of PGC1α and E-cadherin.ConclusionsThe current study demonstrated that HDM disrupted the airway barrier function through the PAR2/TLR4/PGC-1α-dependent pathway. The modulation of this pathway could be a new approach for the treatment of asthma.

Dataset Information

Shear stress regulates aquaporin-5 and airway epithelial barrier function.

Publications

Shear stress regulates aquaporin-5 and airway epithelial barrier function.

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