title: Esophageal ATP synthase and keratinocyte growth factor gene expression changes after acid and bile-induced mucosal damage.
abstract: OBJECTIVE
  Intramural gene expression changes may be critically involved in tissue damage, defense and repair after esophageal regurgitation. The aims were to characterize the consequences of short-term exposure to luminal bile, acid, or bile mixed with acid on the beta-ATPase, keratinocyte growth factor 1 (KGF-1) and KGF receptor (KGF-R) expressions within the mucosa and the muscle layer in a large animal model.
  
  
  METHODS
  Esophageal segments of anesthetized dogs were exposed to saline (n = 3), diluted canine bile (n = 6), hydrochloric acid (n = 5) or bile + hydrochloric acid (n = 5), and tissue biopsies were taken at the end of the 180-min observation period. Semiquantitative reverse transcriptase polymerase chain reactions were carried out and the degree of histological damage was evaluated on the 0-16-grade Geisinger scoring scale.
  
  
  RESULTS
  Acid exposure was followed by a significant decrease in the level of beta-ATPase expression in the mucosa, and parallel increases in KGF-1 and KGF-R expression. Corresponding changes in the muscle layer were not significant. Bile alone evoked more severe tissue damage, with significantly decreased beta-ATPase levels in both the mucosa and the muscle, whereas the KGF-1 expression did not change significantly. The bile + acid treatment induced an intermediate state, with significant beta-ATPase transcription level decreases in both layers, while the mucosal KGF-1 expression was lower than that following acid treatment alone.
  
  
  CONCLUSIONS
  The acid-induced transcriptional level downregulation of mucosal beta-ATPase gene expression in the smooth muscle layer was exacerbated by bile, but the concomitant KGF and KGF-R gene expression changes may indicate the start of a consecutive repair process.
authors.affiliation: Institute of Surgical Research, University of Szeged, P.O. Box 427, 6701, Szeged, Hungary.
authors.forename: K
authors.initials: K
authors.lastname: Szentpáli
authors.forename: A
authors.initials: A
authors.lastname: Paszt
authors.forename: G
authors.initials: G
authors.lastname: Lázár
authors.forename: M
authors.initials: M
authors.lastname: Széll
authors.forename: L
authors.initials: L
authors.lastname: Kemény
authors.forename: A
authors.initials: A
authors.lastname: Dobozy
authors.forename: J
authors.initials: J
authors.lastname: Kaszaki
authors.forename: L
authors.initials: L
authors.lastname: Tiszlavicz
authors.forename: L
authors.initials: L
authors.lastname: Iván
authors.forename: M
authors.initials: M
authors.lastname: Boros
mesh_terms: D025181:ATP Synthetase Complexes / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D004285:Dogs; D004935:Esophageal Diseases / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D004947:Esophagus / Q000201:enzymology; D016220:Fibroblast Growth Factor 1 / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006851:Hydrochloric Acid / Q000494:pharmacology*; D009092:Mucous Membrane / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics
chemical_list: D001647:Bile Acids and Salts; D016220:Fibroblast Growth Factor 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; C065104:keratinocyte growth factor receptor; D025181:ATP Synthetase Complexes; D006851:Hydrochloric Acid