Bile Salts at Low pH Cause Dilation of Intercellular Spaces in In Vitro Stratified Primary Esophageal Cells, Possibly by Modulating Wnt Signaling.

Background: The presence of dilated intercellular spaces in the stratified squamous lining of the esophagus is the pathognomonic feature of reflux esophagitis secondary to gastroesophageal reflux disease (GERD). In addition to stomach acid, bile salts are major constituents of gastroesophageal refluxate. The aim of our study was to determine the effect of bile salts cocktail at different pHs on epithelial junctions in an in vitro transwell model of stratified esophageal squamous epithelium.

Bile acid at low pH reduces squamous differentiation and activates EGFR signaling in esophageal squamous cells in 3-D culture.

Background: Barrett's esophagus is a preneoplastic metaplasia in which the normal squamous epithelium of the esophagus changes to an intestinal, columnar phenotype due to long-term gastro-esophageal reflux. The major components of this reflux are bile and stomach acid. Previous in vitro studies on the effect of bile and acid on esophageal cells have predominantly relied on transformed esophageal squamous cells or cancer cells grown in monolayer culture.

Bile exposure inhibits expression of squamous differentiation genes in human esophageal epithelial cells.

Objective: This study aimed to identify pathways and cellular processes that are modulated by exposure of normal esophageal cells to bile and acid.

Background: Barrett's esophagus most likely develops as a response of esophageal stem cells to the abnormal reflux environment. Although insights into the underlying molecular mechanisms are slowly emerging, much of the metaplastic process remains unknown.

Early G₁ cyclin-dependent kinases as prognostic markers and potential therapeutic targets in esophageal adenocarcinoma.

Purpose: Chromosomal gain at 7q21 is a frequent event in esophageal adenocarcinoma (EAC). However, this event has not been mapped with fine resolution in a large EAC cohort, and its association with clinical endpoints and functional relevance are unclear.

Experimental Design: We used a cohort of 116 patients to fine map the 7q21 amplification using SNP microarrays.

Pathogenesis of Barrett's esophagus: bile acids inhibit the Notch signaling pathway with induction of CDX2 gene expression in human esophageal cells.

Background: Barrett's esophagus (BE) is the predominant risk factor for the development of esophageal adenocarcinoma. BE is characterized by intestinal metaplasia with goblet cells. Reflux of bile acids is known to induce intestinal metaplasia, but the mechanisms are unclear.

Bile acid alone, or in combination with acid, induces CDX2 expression through activation of the epidermal growth factor receptor (EGFR).

Objectives: Bile acids and acid are implicated in the development of Barrett's esophagus. Evidence suggests that Barrett's esophagus intestinal metaplasia may occur via induction of caudal homeobox gene 2 (CDX2). We hypothesized that induction of CDX2 by bile acids may be due to ligand-dependent transactivation of epidermal growth factor receptor (EGFR).

In human entrocytes, GLN transport and ASCT2 surface expression induced by short-term EGF are MAPK, PI3K, and Rho-dependent.

Glutamine, a key nutrient for the enterocyte, is transported among other proteins by ASCT2. Epidermal growth factor (EGF) augments intestinal adaptation. We hypothesized that short-term treatment of human enterocytes with EGF enhances glutamine transport by increasing membranal ASCT2.

Epidermal growth factor and/or growth hormone induce differential, side-specific signal transduction protein phosphorylation in enterocytes.

Background: Epidermal growth factor (EGF) plus growth hormone (GH) enhances luminal glutamine transport into rabbit and human intestinal cells. Our objective was to screen for activation status of signal proteins in C2(BBe)1 cells (enterocyte-like cell line) in response to side-specific EGF or GH treatment and to investigate the dependence of EGF receptor (EGFR) phosphorylation status on its tyrosine kinase.

Methods: C2(BBe)1 cells on Transwells were treated for 15 minutes on either the basolateral or apical-side with EGF or GH.

Macroarray analysis reveals a strain-induced oxidant response in pulmonary epithelial cells.

Mechanical strain initiates a variety of responses in pulmonary epithelial cells. The signaling pathways and molecular alterations leading to these responses remain unclear To identify novel signal transduction pathways activated by strain, macroarray analysis was performed on strained pulmonary epithelial cells. Glutathione S-transferase (GST) pi, GST mu, and heat shock protein (HSP)-27 were increased by strain.

ATB0/ASCT2 expression in residual rabbit bowel is decreased after massive enterectomy and is restored by growth hormone treatment.

Two weeks after 70% enterectomy, glutamine (Gln) transport is downregulated in rabbit residual bowel due to a decrease in system B(0) activity. Providing epidermal growth factor (EGF) and growth hormone (GH) restores Gln transport by increasing systems A and B(0,+) activities. We hypothesized that changes in Na(+)-dependent broad-spectrum neutral amino acid transporter (ATB(0)/ASCT2) protein and mRNA expression correlate with system B(0) activity.

Growth hormone and epidermal growth factor together enhance amino acid transport systems B0,+ and A in remnant small intestine after massive enterectomy.

Background: Sodium-dependent brush-border nutrient transport is decreased 2 weeks after massive enterectomy. This down-regulation is ameliorated by a 1-week infusion of parenteral growth hormone (GH) and epidermal growth factor (EGF) started 1 week after resection. We hypothesize that glutamine (GLN) transport will be enhanced by earlier and longer growth factor infusion, with differential effects on the Na(+)-dependent GLN transport systems A, B(0,+), and B(0)/ASCT2.

Growth hormone and epidermal growth factor together enhance amino acid transport systems B(0,+) and A in remnant small intestine after massive enterectomy.

Background: Sodium-dependent brush border nutrient transport is decreased 2 weeks after massive enterectomy. This downregulation is ameliorated by a 1-week infusion of parenteral growth hormone (GH) and epidermal growth factor (EGF) started 1 week after resection. We hypothesized that glutamine (GLN) transport would be enhanced by earlier and longer growth factor infusion, with differential effects on the Na(+)-dependent GLN transport systems A, B(0,+), and B0/ASCT2.