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Role of E-cadherin in the pathogenesis of gastroesophageal reflux disease.

Publication ,  Journal Article
Jovov, B; Que, J; Tobey, NA; Djukic, Z; Hogan, BLM; Orlando, RC
Published in: Am J Gastroenterol
June 2011

OBJECTIVES: An early event in the pathogenesis of gastroesophageal reflux disease (GERD) is an acid-induced increase in junctional (paracellular) permeability in esophageal epithelium (EE). The molecular events that account for this change are unknown. E-cadherin is a junctional protein important in barrier function in EE. Therefore, defects in barrier function in EE were sought in GERD as well as whether their presence correlated with abnormalities in e-cadherin. METHODS: Endoscopic biopsies of EE from GERD (n=20; male 10; female 10; mean age 50 ± 10 years) and subjects with a healthy esophagus (controls; n=23; male 11; female 12; mean age 51 ± 11 years) were evaluated in mini-Ussing chambers and by western blot and immunochemistry; and serum analyzed by enzyme-linked immunosorbent assay (ELISA). A role for e-cadherin was also assessed using a unique conditional knockout of e-cadherin in adult mouse esophagus. RESULTS: EE from GERD patients had lower electrical resistance and higher fluorescein flux than EE from controls; and the findings in GERD associated with cleavage of e-cadherin. Cleavage of e-cadherin in GERD was documented in EE by the presence of a 35-kDa, C-terminal fragment of the molecule on western blot and by an increase in soluble N-terminal fragments of the molecule in serum. Activation of the membrane metalloproteinase, A Disintegrin And Metalloproteinase (ADAM-10), was identified as a likely cause for cleavage of e-cadherin by western blot and immunostaining and a role for e-cadherin in the increased junctional permeability in EE from GERD supported by showing increased permeability after deletion of e-cadherin in mouse EE. CONCLUSIONS: The EE in GERD has increased junctional permeability and this is in association with proteolytic cleavage of e-cadherin. As loss of e-cadherin can, alone, account for the increase in junctional permeability, cleavage of e-cadherin likely represents a critical molecular event in the pathogenesis of GERD, and identification of cleaved fragments may, if confirmed in larger studies, be valuable as a biomarker of GERD.

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Published In

Am J Gastroenterol

DOI

EISSN

1572-0241

Publication Date

June 2011

Volume

106

Issue

6

Start / End Page

1039 / 1047

Location

United States

Related Subject Headings

  • Severity of Illness Index
  • Sensitivity and Specificity
  • Reverse Transcriptase Polymerase Chain Reaction
  • Reference Values
  • Prognosis
  • Middle Aged
  • Mice, Knockout
  • Mice
  • Male
  • Immunohistochemistry
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Jovov, B., Que, J., Tobey, N. A., Djukic, Z., Hogan, B. L. M., & Orlando, R. C. (2011). Role of E-cadherin in the pathogenesis of gastroesophageal reflux disease. Am J Gastroenterol, 106(6), 1039–1047. https://doi.org/10.1038/ajg.2011.102
Jovov, Biljana, Jianwen Que, Nelia A. Tobey, Zorka Djukic, Brigid L. M. Hogan, and Roy C. Orlando. “Role of E-cadherin in the pathogenesis of gastroesophageal reflux disease.Am J Gastroenterol 106, no. 6 (June 2011): 1039–47. https://doi.org/10.1038/ajg.2011.102.
Jovov B, Que J, Tobey NA, Djukic Z, Hogan BLM, Orlando RC. Role of E-cadherin in the pathogenesis of gastroesophageal reflux disease. Am J Gastroenterol. 2011 Jun;106(6):1039–47.
Jovov, Biljana, et al. “Role of E-cadherin in the pathogenesis of gastroesophageal reflux disease.Am J Gastroenterol, vol. 106, no. 6, June 2011, pp. 1039–47. Pubmed, doi:10.1038/ajg.2011.102.
Jovov B, Que J, Tobey NA, Djukic Z, Hogan BLM, Orlando RC. Role of E-cadherin in the pathogenesis of gastroesophageal reflux disease. Am J Gastroenterol. 2011 Jun;106(6):1039–1047.

Published In

Am J Gastroenterol

DOI

EISSN

1572-0241

Publication Date

June 2011

Volume

106

Issue

6

Start / End Page

1039 / 1047

Location

United States

Related Subject Headings

  • Severity of Illness Index
  • Sensitivity and Specificity
  • Reverse Transcriptase Polymerase Chain Reaction
  • Reference Values
  • Prognosis
  • Middle Aged
  • Mice, Knockout
  • Mice
  • Male
  • Immunohistochemistry