Differences in ERK activation in squamous mucosa in patients who have gastroesophageal reflux disease with and without Barrett's esophagus

Rhonda F. Souza, Kenneth L. Shewmake, Yuenan Shen, Ruben D. Ramirez, Jeff S. Bullock, Christa L. Hladik, Edward L. Lee, Lance S. Terada, Stuart J. Spechler

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

OBJECTIVES: In some patients with gastroesophageal reflux disease (GERD), the reflux-damaged esophageal squamous epithelium heals through the process of intestinal metaplasia (resulting in Barrett's esophagus) rather than through the regeneration of more squamous cells. We hypothesized that squamous epithelium in Barrett's esophagus might have abnormalities in activation of the extracellular-regulated kinases 1 and 2 (ERK1/2) signaling pathway that may facilitate esophageal repair through metaplasia in response to acid-induced injury. METHODS: Endoscopic biopsies were taken from distal esophageal squamous mucosa in patients who had GERD with and without Barrett's esophagus and in controls, before and after esophageal perfusion with 0.1 N HC1 acid. Basal ERK1/2 phosphorylation, acid-induced ERK1/2 activity and phosphorylation, and localization of phosphorylated ERK1/2 were determined using immunoblotting, Western blotting, and immunohistochemistry. RESULTS: Compared to patients with Barrett's esophagus, patients with GERD exhibited significantly lower baseline levels of phosphorylated ERK1/2 expression (35 ± 4% vs 90 ± 21% control, p = 0.01) Acid exposure significantly increased ERK1/2 activity (346.6 ± 51.90 to 446.8 ± 62.44 RIU, p = 0.02) and phosphorylation (3.55 ± 1.26 to 4.49 ± 1.25 [ratio phospho/total ERK], p = 0.01) in the squamous mucosa of GERD patients, but not in those with Barrett's esophagus or in controls. CONCLUSIONS: Between patients with Barrett's esophagus and patients with uncomplicated GERD, there are significant differences in baseline levels and in acid-induced activation of ERK1/2 in esophageal squamous epithelium. To our knowledge, this is the first description of a molecular, phenotypic feature that distinguishes the esophageal squamous mucosa of GERD patients with and without Barrett's esophagus.

Original languageEnglish (US)
Pages (from-to)551-559
Number of pages9
JournalAmerican Journal of Gastroenterology
Volume100
Issue number3
DOIs
StatePublished - Mar 2005

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Barrett Esophagus
Gastroesophageal Reflux
Mucous Membrane
Phosphotransferases
Acids
Epithelium
Phosphorylation
Metaplasia
Immunoblotting
Regeneration
Perfusion
Western Blotting
Epithelial Cells
Immunohistochemistry
Biopsy
Wounds and Injuries

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Differences in ERK activation in squamous mucosa in patients who have gastroesophageal reflux disease with and without Barrett's esophagus. / Souza, Rhonda F.; Shewmake, Kenneth L.; Shen, Yuenan; Ramirez, Ruben D.; Bullock, Jeff S.; Hladik, Christa L.; Lee, Edward L.; Terada, Lance S.; Spechler, Stuart J.

In: American Journal of Gastroenterology, Vol. 100, No. 3, 03.2005, p. 551-559.

Research output: Contribution to journalArticle

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abstract = "OBJECTIVES: In some patients with gastroesophageal reflux disease (GERD), the reflux-damaged esophageal squamous epithelium heals through the process of intestinal metaplasia (resulting in Barrett's esophagus) rather than through the regeneration of more squamous cells. We hypothesized that squamous epithelium in Barrett's esophagus might have abnormalities in activation of the extracellular-regulated kinases 1 and 2 (ERK1/2) signaling pathway that may facilitate esophageal repair through metaplasia in response to acid-induced injury. METHODS: Endoscopic biopsies were taken from distal esophageal squamous mucosa in patients who had GERD with and without Barrett's esophagus and in controls, before and after esophageal perfusion with 0.1 N HC1 acid. Basal ERK1/2 phosphorylation, acid-induced ERK1/2 activity and phosphorylation, and localization of phosphorylated ERK1/2 were determined using immunoblotting, Western blotting, and immunohistochemistry. RESULTS: Compared to patients with Barrett's esophagus, patients with GERD exhibited significantly lower baseline levels of phosphorylated ERK1/2 expression (35 ± 4{\%} vs 90 ± 21{\%} control, p = 0.01) Acid exposure significantly increased ERK1/2 activity (346.6 ± 51.90 to 446.8 ± 62.44 RIU, p = 0.02) and phosphorylation (3.55 ± 1.26 to 4.49 ± 1.25 [ratio phospho/total ERK], p = 0.01) in the squamous mucosa of GERD patients, but not in those with Barrett's esophagus or in controls. CONCLUSIONS: Between patients with Barrett's esophagus and patients with uncomplicated GERD, there are significant differences in baseline levels and in acid-induced activation of ERK1/2 in esophageal squamous epithelium. To our knowledge, this is the first description of a molecular, phenotypic feature that distinguishes the esophageal squamous mucosa of GERD patients with and without Barrett's esophagus.",
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T1 - Differences in ERK activation in squamous mucosa in patients who have gastroesophageal reflux disease with and without Barrett's esophagus

AU - Souza, Rhonda F.

AU - Shewmake, Kenneth L.

AU - Shen, Yuenan

AU - Ramirez, Ruben D.

AU - Bullock, Jeff S.

AU - Hladik, Christa L.

AU - Lee, Edward L.

AU - Terada, Lance S.

AU - Spechler, Stuart J.

PY - 2005/3

Y1 - 2005/3

N2 - OBJECTIVES: In some patients with gastroesophageal reflux disease (GERD), the reflux-damaged esophageal squamous epithelium heals through the process of intestinal metaplasia (resulting in Barrett's esophagus) rather than through the regeneration of more squamous cells. We hypothesized that squamous epithelium in Barrett's esophagus might have abnormalities in activation of the extracellular-regulated kinases 1 and 2 (ERK1/2) signaling pathway that may facilitate esophageal repair through metaplasia in response to acid-induced injury. METHODS: Endoscopic biopsies were taken from distal esophageal squamous mucosa in patients who had GERD with and without Barrett's esophagus and in controls, before and after esophageal perfusion with 0.1 N HC1 acid. Basal ERK1/2 phosphorylation, acid-induced ERK1/2 activity and phosphorylation, and localization of phosphorylated ERK1/2 were determined using immunoblotting, Western blotting, and immunohistochemistry. RESULTS: Compared to patients with Barrett's esophagus, patients with GERD exhibited significantly lower baseline levels of phosphorylated ERK1/2 expression (35 ± 4% vs 90 ± 21% control, p = 0.01) Acid exposure significantly increased ERK1/2 activity (346.6 ± 51.90 to 446.8 ± 62.44 RIU, p = 0.02) and phosphorylation (3.55 ± 1.26 to 4.49 ± 1.25 [ratio phospho/total ERK], p = 0.01) in the squamous mucosa of GERD patients, but not in those with Barrett's esophagus or in controls. CONCLUSIONS: Between patients with Barrett's esophagus and patients with uncomplicated GERD, there are significant differences in baseline levels and in acid-induced activation of ERK1/2 in esophageal squamous epithelium. To our knowledge, this is the first description of a molecular, phenotypic feature that distinguishes the esophageal squamous mucosa of GERD patients with and without Barrett's esophagus.

AB - OBJECTIVES: In some patients with gastroesophageal reflux disease (GERD), the reflux-damaged esophageal squamous epithelium heals through the process of intestinal metaplasia (resulting in Barrett's esophagus) rather than through the regeneration of more squamous cells. We hypothesized that squamous epithelium in Barrett's esophagus might have abnormalities in activation of the extracellular-regulated kinases 1 and 2 (ERK1/2) signaling pathway that may facilitate esophageal repair through metaplasia in response to acid-induced injury. METHODS: Endoscopic biopsies were taken from distal esophageal squamous mucosa in patients who had GERD with and without Barrett's esophagus and in controls, before and after esophageal perfusion with 0.1 N HC1 acid. Basal ERK1/2 phosphorylation, acid-induced ERK1/2 activity and phosphorylation, and localization of phosphorylated ERK1/2 were determined using immunoblotting, Western blotting, and immunohistochemistry. RESULTS: Compared to patients with Barrett's esophagus, patients with GERD exhibited significantly lower baseline levels of phosphorylated ERK1/2 expression (35 ± 4% vs 90 ± 21% control, p = 0.01) Acid exposure significantly increased ERK1/2 activity (346.6 ± 51.90 to 446.8 ± 62.44 RIU, p = 0.02) and phosphorylation (3.55 ± 1.26 to 4.49 ± 1.25 [ratio phospho/total ERK], p = 0.01) in the squamous mucosa of GERD patients, but not in those with Barrett's esophagus or in controls. CONCLUSIONS: Between patients with Barrett's esophagus and patients with uncomplicated GERD, there are significant differences in baseline levels and in acid-induced activation of ERK1/2 in esophageal squamous epithelium. To our knowledge, this is the first description of a molecular, phenotypic feature that distinguishes the esophageal squamous mucosa of GERD patients with and without Barrett's esophagus.

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