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Extracellular Matrix Influences Alveolar Epithelial Claudin Expression and Barrier Function

¹ Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, and ² Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia; ³ Veterans Affairs Medical Center, Atlanta, Georgia; and ⁴ Department of Physiology, Emory University School of Medicine, Atlanta, Georgia

Correspondence and requests for reprints should be addressed to Michael Koval, Ph.D., or Jesse Roman, M.D., Emory University School of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Whitehead Biomedical Research Building, 615 Michael St., Suite 205, Atlanta, GA 30322. E-mail: mhkoval{at}emory.edu or j.roman{at}louisville.edu

The lung is dynamically remodeled in response to injury, which alters extracellular matrix composition, and can lead to either healthy or impaired lung regeneration. To determine how changes in extracellular matrix can influence alveolar epithelial barrier function, we examined the expression and function of tight junction proteins by rat alveolar epithelial type II cells cultured on one of three different matrix components: type I collagen or fibronectin, matrix glycoproteins which are highly expressed in injured lungs, or laminin, a basement membrane matrix component. Of note, alveolar epithelial cells cultured for 2 days on fibronectin formed high-resistance barriers and showed continuous claudin-3 and claudin-18 localization to the plasma membrane, as opposed to cells cultured on either type I collagen or laminin, which had low resistance monolayers and had areas of cell–cell contact that were claudin deficient. The barrier formed by cells cultured on fibronectin also had preferential permeability to chloride as compared with sodium. Regardless of the initial matrix composition, alveolar epithelial cells cultured for 5 days formed high-resistance barriers, which correlated with increased claudin-18 localization to the plasma membrane and an increase in zonula occludens-1. Day 5 cells on laminin had significantly higher resistance than cells on either fibronectin or type I collagen. Thus, although alveolar epithelial cells on fibronectin formed rapid barriers, it was at the expense of producing an optimized barrier.

Key Words: tight junction • claudin • basement membrane • lung injury • fibronectin

CLINICAL RELEVANCE A fibronectin-enriched provisional matrix accumulates during acute lung injury. We found that, although fibronectin promoted rapid reformation of alveolar barriers, these were suboptimal as compared with barriers more slowly produced by cells on healthy matrix.

 

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