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Digestive Diseases and Sciences

, Volume 61, Issue 6, pp 1524–1533 | Cite as

Tight Junction Ultrastructure Alterations in a Mouse Model of Enteral Nutrient Deprivation

  • Farokh R. DemehriEmail author
  • Susanne M. Krug
  • Yongjia Feng
  • In-Fah M. Lee
  • Joerg D. Schulzke
  • Daniel H. Teitelbaum
Original Article

Abstract

Background

Total parenteral nutrition (TPN), a necessary treatment for patients who cannot receive enteral nutrition, is associated with infectious complications due in part to a loss of intestinal epithelial barrier function (EBF). Using a mouse model of TPN, with enteral nutrient deprivation, we previously demonstrated an increase in mucosal interferon-γ and tumor necrosis factor-α; these cytokine changes are a major mediator driving a reduction in epithelial tight junction (TJ) protein expression. However, the exact ultrastructural changes to the intestinal epithelial barrier have not been previously described.

Aim

We hypothesized that TPN dependence results in ultrastructural changes in the intestinal epithelial TJ meshwork.

Methods

C57BL/6 mice underwent internal jugular venous cannulation and were given enteral nutrition or TPN with enteral nutrient deprivation for 7 days. Freeze-fracture electron microscopy was performed on ileal tissue to characterize changes in TJ ultrastructure. EBF was measured using transepithelial resistance and tracer permeability, while TJ expression was measured via Western immunoblotting and immunofluorescence staining.

Results

While strand density, linearity, and appearance were unchanged, TPN dependence led to a mean reduction in one horizontal strand out of the TJ compact meshwork to a more basal region, resulting in a reduction in meshwork depth. These findings were correlated with the loss of TJ localization of claudin-4 and tricellulin, reduced expression of claudin-5 and claudin-8, and reduced ex vivo EBF.

Conclusion

Tight junction ultrastructural changes may contribute to reduced EBF in the setting of TPN dependence.

Keywords

Small intestine Parenteral nutrition Epithelial barrier function Tight junction Freeze-fracture electron microscopy 

Notes

Acknowledgments

This work was supported by the US National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases 5R01AI-44076-15 (to DHT).

Compliance with ethical standards

Conflict of interest

None.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Section of Pediatric Surgery, Department of SurgeryMott Children’s Hospital, University of Michigan Health SystemAnn ArborUSA
  2. 2.Institute of Clinical PhysiologyCharité – Universitätsmedizin BerlinBerlinGermany

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