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The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
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Polyamines regulate E-cadherin transcription through c-Myc modulating intestinal epithelial barrier function.

Lan Liu1, Xin Guo, Jaladanki N Rao

  • 1Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.

American Journal of Physiology. Cell Physiology
|January 30, 2009
PubMed
Summary

Polyamines boost intestinal barrier integrity by increasing E-cadherin expression through the transcription factor c-Myc. This mechanism is crucial for maintaining epithelial barrier function and preventing dysfunction.

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Area of Science:

  • Cell Biology
  • Gastroenterology
  • Molecular Biology

Background:

  • Intestinal epithelial barrier integrity relies on intercellular junctions, with E-cadherin at adherens junctions mediating cell-cell contacts.
  • Polyamines are essential for E-cadherin expression, but the precise molecular mechanisms remain unclear.

Purpose of the Study:

  • To investigate if polyamines induce E-cadherin expression via the transcription factor c-Myc.
  • To determine the role of polyamine-regulated E-cadherin in maintaining intestinal epithelial barrier integrity.

Main Methods:

  • Assessed the impact of polyamine levels on c-Myc and E-cadherin transcription using promoter activity assays and mRNA analysis.
  • Utilized adenoviral vectors for forced c-Myc expression in polyamine-deficient cells.
  • Employed E-cadherin promoter mutants and small interfering RNA (siRNA) to elucidate regulatory pathways and barrier function.

Main Results:

  • Reduced polyamines decreased c-Myc and repressed E-cadherin transcription, lowering promoter activity and mRNA levels.
  • Forced c-Myc expression restored E-cadherin transcription and protein levels in polyamine-deficient cells.
  • Polyamines enhance E-cadherin transcription via the E-Pal box in the E-cadherin promoter, mediated by c-Myc.

Conclusions:

  • Polyamines enhance E-cadherin transcription by activating c-Myc, thereby promoting intestinal epithelial barrier function.
  • Polyamines are critical for maintaining epithelial barrier integrity, particularly under stress conditions like H(2)O(2) exposure.