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Sphingosine-1-Phosphate Regulates the Expression of Adherens Junction Protein E-Cadherin and Enhances Intestinal Epithelial Cell Barrier Function

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Abstract

Background

The regulation of intestinal barrier permeability is important in the maintenance of normal intestinal physiology. Sphingosine-1-phosphate (S1P) has been shown to play a pivotal role in enhancing barrier function in several non-intestinal tissues. The current study determined whether S1P regulated function of the intestinal epithelial barrier by altering expression of E-cadherin, an important protein in adherens junctions.

Methods

Studies were performed upon cultured differentiated IECs (IEC-Cdx2L1 line) using standard techniques.

Results

S1P treatment significantly increased levels of E-cadherin protein and mRNA in intestinal epithelial cells (IECs) and also led to E-cadherin localizing strongly to the cell–cell border. S1P also improved the barrier function as indicated by a decrease in 14C-mannitol paracellular permeability and an increase in transepithelial electrical resistance (TEER) in vitro.

Conclusions

These results indicate that S1P increases levels of E-cadherin, both in cellular amounts and at the cell–cell junctions, and leads to improved barrier integrity in cultured intestinal epithelial cells.

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Acknowledgments

This work was supported by a Research Career Development Award and a VA Merit Award (to D.J.T.) from the Department of Veterans Affairs.

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Authors and Affiliations

  1. Department of Surgery, Baltimore Veterans Affairs Medical Center, 10 N. Greene Street, Baltimore, MD, 21201, USA

    Ruiyun Li, Lan Xiao, Jaladanki N. Rao, Jian-Ying Wang & Douglas J. Turner

  2. Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA

    Jose Greenspon, Ruiyun Li, Lan Xiao, Jaladanki N. Rao, Eric D. Strauch, Jian-Ying Wang & Douglas J. Turner

  3. Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA

    Jian-Ying Wang

  4. Department of Gastroenterology, University of Maryland School of Medicine, Baltimore, MD, USA

    Rex Sun & Terez Shea-Donohue

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  1. Jose Greenspon
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  2. Ruiyun Li
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Correspondence to Douglas J. Turner.

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Greenspon, J., Li, R., Xiao, L. et al. Sphingosine-1-Phosphate Regulates the Expression of Adherens Junction Protein E-Cadherin and Enhances Intestinal Epithelial Cell Barrier Function. Dig Dis Sci 56, 1342–1353 (2011). https://doi.org/10.1007/s10620-010-1421-0

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