Shear stress regulates aquaporin-5 and airway epithelial barrier function

doi:10.1073/pnas.0712287105

Shear stress regulates aquaporin-5 and airway epithelial barrier function

*Department of Medicine, Division of Pulmonary and Critical Care Medicine, and
Departments of ^‡Biological Chemistry and
^§Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205

Communicated by Peter C. Agre, Duke University, Durham, NC, December 27, 2007 (received for review December 11, 2007)

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.

Footnotes

^†To whom correspondence should be addressed. E-mail: vsidhay1{at}jhmi.edu
Author contributions: V.K.S. designed research; V.K.S. and K.S.S. performed research; V.K.S., M.J.C., and L.S. contributed new reagents/analytic tools; V.K.S., L.S., and L.S.K. analyzed data; and V.K.S. and L.S.K. wrote the paper.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/cgi/content/full/0712287105/DC1.