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Sensing of Barrier Tissue Disruption with an Organic Electrochemical Transistor
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Defective barrier function in neosquamous epithelium.

Biljana Jovov1, Nicholas J Shaheen, Geraldine S Orlando

  • 1Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599-7032, USA. bjovov@med.unc.edu

The American Journal of Gastroenterology
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Summary

Neosquamous epithelium (NSE) after radiofrequency ablation (RFA) for Barrett's esophagus has a defective barrier function, making it vulnerable to reflux injury and potentially explaining Barrett's esophagus recurrence after ablation.

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Area of Science:

  • Gastroenterology
  • Oncology
  • Epithelial Biology

Background:

  • Radiofrequency ablation (RFA) is used to treat Barrett's esophagus (BE), aiming to prevent esophageal adenocarcinoma (EAC).
  • Following RFA, a new squamous lining, termed neosquamous epithelium (NSE), forms.
  • The protective capacity of NSE against ongoing reflux is not well understood.

Purpose of the Study:

  • To compare the barrier function of NSE with native upper squamous epithelium (USE).
  • To investigate the histological and molecular characteristics of NSE barrier function.

Main Methods:

  • Endoscopic biopsies from RFA-treated subjects were analyzed.
  • Barrier function was assessed using electrical resistance and fluorescein flux in mini-Ussing chambers.
  • Claudin expression in tight junctions was quantified using qPCR and immunoblots.

Main Results:

  • NSE exhibited histological abnormalities, including dilated intercellular spaces and eosinophilia.
  • NSE demonstrated significantly higher permeability (lower electrical resistance, higher fluorescein flux) than USE and controls.
  • Defective NSE permeability was linked to reduced expression of claudin-4 and claudin-10.

Conclusions:

  • Neosquamous epithelium frequently displays impaired barrier function.
  • This defect renders NSE susceptible to injury from refluxate, potentially contributing to BE recurrence post-ablation.