Acidic duodenal pH alters gene expression in the cystic fibrosis mouse pancreas.
The duodenum is abnormally acidic in cystic fibrosis (CF) due to decreased bicarbonate ion secretion that is dependent on the CF gene product CFTR. In the CFTR null mouse, the acidic duodenum results in increased signaling from the intestine to the exocrine pancreas in an attempt to stimulate pancreatic bicarbonate ion secretion. Excess stimulation is proposed to add to the stress/inflammation of the pancreas in CF. DNA microarray analysis of the CF mouse revealed altered pancreatic gene expression characteristic of stress/inflammation. When the duodenal pH was corrected genetically (crossing CFTR null with gastrin null mice) or pharmacologically (use of the proton pump inhibitor omeprazole), expression levels of genes measured by quantitative RT-PCR were significantly normalized. It is concluded that the acidic duodenal pH in CF contributes to the stress on the exocrine pancreas and that normalizing duodenal pH reduces this stress.
Kaur
Simran
S
Dept. of Anatomy and Cell Biology, Univ. of Kansas School of Medicine, Kansas City, KS 66160, USA.
Norkina
Oxana
O
Ziemer
Donna
D
Samuelson
Linda C
LC
De Lisle
Robert C
RC
D000143:Acids / Q000378:metabolism*; D000681:Amylases / Q000097:blood; D000818:Animals; D002678:Chimera; D003550:Cystic Fibrosis / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000172:deficiency; D004386:Duodenum / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005755:Gastrins / Q000172:deficiency; D015870:Gene Expression / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D009853:Omeprazole / Q000494:pharmacology; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010195:Pancreatitis / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000143:Acids; D004791:Enzyme Inhibitors; D005755:Gastrins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000681:Amylases; D009853:Omeprazole