The secretory phospholipase A2 gene is required for gastroesophageal reflux-related changes in murine esophagus.
BACKGROUND
The initial response of esophageal mucosa to gastroduodenal reflux is inflammation and hyperplasia. Secretory phospholipase A(2) (sPLA(2)) is a known mediator of gut inflammation, and its levels are increased in Barrett's esophagus. We hypothesized that the sPLA(2) gene is required to produce esophageal mucosal hyperplasia in response to gastroduodenal reflux.


METHODS
C57BL/6 (n = 5) sPLA(2) (-/-) mice and C57BL/6( Cg-Tg(PLA2G2A)703N16 ) mice (n = 4) sPLA(2) (-/+) underwent a side-to-side surgical anastomosis between the duodenum and gastroesophageal junction (DGEA). Control animals [sPLA(2) (-/-) (n = 5), sPLA(2) (-/+) (n = 4)] underwent laparotomy with incision and repair of the esophagus. Tissue was harvested after 4 weeks, and H&E staining was performed to quantify esophageal mucosal thickness. Ki67 and sPLA(2) immunostaining were performed to quantitate differences in cell division and sPLA(2) expression.


RESULTS
Mice expressing human sPLA(2) had a 2.5-fold increase in thickness of the esophageal mucosa as compared to controls (p = 0.01). A 6.5-fold increase in proliferation (p = 0.02) and a twofold increase in sPLA(2) expression (p = 0.04) were demonstrated in animals exposed to gastroduodenal reflux.


CONCLUSIONS
The presence of sPLA(2) is necessary for early mucosal hyperplasia produced by exposure of the esophagus to gastroduodenal contents. sPLA(2) expression is upregulated by gastroduodenal reflux, strengthening its role as a critical mediator of early mucosal hyperplasia.
Babu
Ashok
A
Division of Cardiothoracic Surgery, Department of Surgery, University of Colorado Denver School of Medicine Aurora, 12631 East 17th Avenue, C310, Aurora, CO 80045, USA.
Mauchley
David
D
Meng
Xianzhong
X
Banerjee
Anirban M
AM
Gamboni-Robertson
Fabia
F
Fullerton
David A
DA
Weyant
Michael J
MJ
D000818:Animals; D002455:Cell Division; D004383:Duodenogastric Reflux / Q000378:metabolism / Q000473:pathology; D004947:Esophagus / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D005764:Gastroesophageal Reflux / Q000473:pathology*; D015870:Gene Expression; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000473:pathology; D054497:Phospholipases A2, Secretory / Q000032:analysis / Q000235:genetics*
D054497:Phospholipases A2, Secretory