Article

Developmental regulation of claudin localization by fetal alveolar epithelial cells

The Children's Hospital of Philadelphia, Filadelfia, Pennsylvania, United States
AJP Lung Cellular and Molecular Physiology (Impact Factor: 4.04). 12/2004; 287(6):L1266-73. DOI: 10.1152/ajplung.00423.2003
Source: PubMed

ABSTRACT Tight junction proteins in the claudin family regulate epithelial barrier function. We examined claudin expression by human fetal lung (HFL) alveolar epithelial cells cultured in medium containing dexamethasone, 8-bromo-cAMP, and isobutylmethylxanthanine (DCI), which promotes alveolar epithelial cell differentiation to a type II phenotype. At the protein level, HFL cells expressed claudin-1, claudin-3, claudin-4, claudin-5, claudin-7, and claudin-18, where levels of expression varied with culture conditions. DCI-treated differentiated HFL cells cultured on permeable supports formed tight transepithelial barriers, with transepithelial resistance (TER) >1,700 ohm/cm(2). In contrast, HFL cells cultured in control medium without DCI did not form tight barriers (TER <250 ohm/cm(2)). Consistent with this difference in barrier function, claudins expressed by HFL cells cultured in DCI medium were tightly localized to the plasma membrane; however, claudins expressed by HFL cells cultured in control medium accumulated in an intracellular compartment and showed discontinuities in claudin plasma membrane localization. In contrast to claudins, localization of other tight junction proteins, zonula occludens (ZO)-1, ZO-2, and occludin, was not sensitive to HFL cell phenotype. Intracellular claudins expressed by undifferentiated HFL cells were localized to a compartment containing early endosome antigen-1, and treatment of HFL cells with the endocytosis inhibitor monodansylcadaverine increased barrier function. This suggests that during differentiation to a type II cell phenotype, fetal alveolar epithelial cells use differential claudin expression and localization to the plasma membrane to help regulate tight junction permeability.

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    • "Bronchial epithelium also expresses cingulin, ZO-1, ZO-2, and ZO-3 [30] [34]. Occludin, ZO-1, ZO-2, ZO-3, cingulin and JAM-1 are expressed in alveolar cells [30] [35] [36]. "
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    • "Induction of claudin-5 by glucocorticoids has been described in rat brain microvessel endothelial cells (BMEC, GPNT), where addition of hydrocortisone to the cultures resulted in fewer frayed junctions and a more uniform distribution of claudin-5 at the cell borders as compared with cultures without hydrocortisone treatment [26] [44]. In human alveolar epithelial cells, as well as in HUVEC claudin-5 has been shown to be one of the major genes up-regulated during differentiation in culture [14] [45] [46]. Also expression of adherens proteins, such as E-cadherin or VE-cadherin was enhanced by glucocorticoids [47] [48]. "
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    Molecular and Cellular Endocrinology 11/2008; 298(1-2):19-24. DOI:10.1016/j.mce.2008.09.041 · 4.24 Impact Factor
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    • "tion of the TJ protein claudin - 5 at the cell borders as compared with cultures without GC treatment ( Romero et al . 2003 ; Calabria et al . 2006 ) . A recent screen of gene expression by human alveolar epithelial cells indicated that claudin - 5 is one of the major genes up - regulated during differentiation in culture ( Gonzales et al . 2002 ; Daugherty et al . 2004 ) . On the other hand , responsivity of the human VE - cadherin gene to GCs could not be observed in hCMEC / D3 cells , while it represents a GC target in the mouse ( Blecharz et al . 2008 ) . Reports on GC effects on VE - cadherin in other species or tissues could not be found , while the epithelial adherens protein , E - cadherin was "
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