Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017168 (gastroesophageal reflux disease)
 11,783 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytokeratins are subunit proteins of epithelial cell intermediate filaments, which are genetically determined. Because epithelia have their own characteristic cytokeratin profile, this may reveal the origin of the epithelium. The cytokeratin profile of Barrett's oesophagus, complicating severe gastro-oesophageal reflux disease, was determined in 35 consecutive patients and in 10 normal controls in order to provide insight into the origin of Barrett's epithelium. Immunostaining of frozen sections showed abundant immunoactivity for cytokeratin (CK) 13, which is characteristic of squamous epithelia, including that of the oesophagus, but is not present in the simple columnar epithelium of the cardia. On the other hand, the latter epithelium expresses mainly CK 8, 18 and 19, also found in Barrett's epithelium. The presence of CK 13 in Barrett's epithelium may indicate its origin from the squamous oesophageal epithelium and not from the proximal migration of columnar epithelial cells of the gastric cardia.
 ...
PMID:Cytokeratin profile suggests metaplastic epithelial transformation in Barrett's oesophagus. 886 84

Gastroesophageal reflux disease (GERD) clinically predisposes to columnar Barrett's metaplasia (BM) in the distal esophagus. We demonstrate evidence supporting the cellular origin of BM from reprograming or transcommitment of resident normal esophageal squamous (NES) epithelial cells in response to acid and bile (A + B) exposure using an in vitro cell culture model. The hTERT-immortalized NES cell line NES-B10T was exposed 5 min/day to an A + B mixture for 30 wk. Morphological changes, mRNA, and protein expression levels for the inflammatory marker cyclooxygenase-2; the lineage-determining transcription factors TAp63 (squamous), CDX2, and SOX9 (both columnar); and the columnar lineage markers Villin, Muc-2, CK8, and mAb Das-1 (incomplete phenotype of intestinal metaplasia) were assessed every 10 wk. Markers of columnar lineage and inflammation increased progressively, while squamous lineage-determining transcriptional factors were significantly decreased both at the mRNA and/or protein level in the NES-B10T cells at/after A + B treatment for 30 wk. Distinct modifications in morphological features were only observed at/after 30 wk of A + B exposure. These changes acquired by the NES-B10T 30-wk cells were retained even after cessation of A + B exposure for at least 3 wk. This study provides evidence that chronic exposure to the physiological components of gastric refluxate leads to repression of the discernable squamous transcriptional factors and activation of latent columnar transcriptional factors. This reflects the alteration in lineage commitment of the precursor-like biphenotypic, NES-B10T cells in response to A + B exposure as the possible origin of BM from the resident NES cells.NEW & NOTEWORTHY This study provides evidence of the origins of Barrett's metaplasia from lineage transcommitment of resident esophageal cells after chronic exposure to gastroesophageal refluxate. The preterminal progenitor-like squamous cells alter their differentiation and develop biphenotypic characteristics, expressing markers of incomplete-type columnar metaplasia. Development of these biphenotypic precursors in vitro is a unique model to study pathogenesis of Barrett's metaplasia and esophageal adenocarcinoma.
 ...
PMID:Barrett's metaplasia develops from cellular reprograming of esophageal squamous epithelium due to gastroesophageal reflux. 2833 46