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Author Notes:

Address for reprint requests and other correspondence: M. Koval, Emory Univ. School of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Whitehead Biomedical Research Bldg., 615 Michael St., Suite 205, Atlanta, GA 30322 (e-mail: mhkoval@emory.edu).

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Research Funding:

This work was supported by Emory Alcohol and Lung Biology Center/National Institutes of Health (NIH) Grant P50-AA-013757 (M. Koval); NIH Grants R01-HL-083120 (M. Koval), R01-HL-57204 (M. Koval and S. S. Margulies), and AA-013528 (C. E. Overgaard and L. A. Mitchell); and the Emory University Research Committee (M. Koval).

Keywords:

  • tight junction
  • alveolus
  • lung barrier

Differential effects of claudin-3 and claudin-4 on alveolar epithelial barrier function

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Journal Title:

American Journal of Physiology - Lung Cellular and Molecular Physiology

Volume:

Volume 301, Number 1

Publisher:

, Pages L40-L49

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Alveolar barrier function depends critically on the claudin family tight junction proteins. Of the major claudins expressed by alveolar epithelial cells, claudin (Cldn)-3 and Cldn-4 are the most closely related by amino acid homology, yet they differ dramatically in the pattern of expression. Previously published reports have shown that Cldn-3 is predominantly expressed by type II alveolar epithelial cells; Cldn-4 is expressed throughout the alveolar epithelium and is specifically upregulated in response to acute lung injury. Using primary rat alveolar epithelial cells transduced with yellow fluorescent protein-tagged claudin constructs, we have identified roles for Cldn-3 and Cldn-4 in alveolar epithelial barrier function. Surprisingly, increasing expression of Cldn-3 decreased alveolar epithelial barrier function, as assessed by transepithelial resistance and dye flux measurements. Conversely, increasing Cldn-4 expression improved alveolar epithelial transepithelial resistance compared with control cells. Other alveolar epithelial tight junction proteins were largely unaffected by increased expression of Cldn-3 and Cldn-4. Taken together, these results demonstrate that, in the context of the alveolar epithelium, Cldn-3 and Cldn-4 have different effects on paracellular permeability, despite significant homology in their extracellular loop domains.

Copyright information:

© 2011 the American Physiological Society

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