Acidic duodenal pH alters gene expression in the cystic fibrosis mouse pancreas

Acidic duodenal pH alters gene expression in the cystic fibrosis mouse pancreas
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DOI:
10.1152/ajpgi.00035.2004
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发表时间:
2004-08-01
影响因子:
4.5
通讯作者:
De Lisle, RC
De Lisle, RC
中科院分区:
医学2区
文献类型:
--
作者:
Kaur, S;Norkina, O;De Lisle, RC

文献摘要

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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 RTPCR 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.