Publications (2)15.21 Total impact
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Article: Estrogen regulation of duodenal bicarbonate secretion and sex-specific protection of human duodenum.
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ABSTRACT: The reason that women have a lower prevalence of duodenal ulcer is not clear. We investigated whether estrogen regulates human duodenal bicarbonate secretion (DBS) and whether this process accounts for sex differences in the prevalence of duodenal ulcer. We performed an epidemiologic study to correlate duodenal ulcer prevalence with sex and age. Proximal DBS was measured from healthy subjects. Estrogen-receptor expression was examined in human duodenal mucosa by immunoblot and immunohistochemical analyses. Among women, the prevalence of duodenal ulcer was significantly lower than among men. The reduced prevalence was greatest among premenopausal women (20-49 y), who were 3.91- to 5.09-fold less likely to develop duodenal ulcers than age-matched men; the difference was reduced to 1.32-fold or less among subjects aged 60 years or older. Premenopausal (20-29 y), but not postmenopausal (60-69 y), women had significantly higher basal and acid-stimulated DBS than the age-matched men. Basal and acid-stimulated DBS in premenopausal women (20-29 y) were significantly higher than in postmenopausal women (60-69 y), whereas there were no significant differences in basal or acid-stimulated DBS between men who were aged 20-29 years or 60-69 years. Serum levels of estradiol changed in parallel with basal and acid-stimulated DBS during the physiological menstrual cycle in premenopausal women. 17β-estradiol-stimulated DBS was independent of age or sex. Estrogen receptors α and β were detected on plasma membranes and in the cytosol of human duodenal epithelial cells. Estrogen regulates human DBS, which could reduce the risk for duodenal ulcer in women and contribute to sex differences in the prevalence of duodenal ulcer.Gastroenterology 05/2011; 141(3):854-63. · 11.68 Impact Factor -
Article: Involvement of phosphatidylinositol 3-kinase in cAMP- and cGMP-induced duodenal epithelial CFTR activation in mice.
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ABSTRACT: Although phosphatidylinositol 3-kinase (PI3K) is essential for several cellular signal transductions, its role in the regulation of cystic fibrosis transmembrane conductance regulator (CFTR) activity in intestinal epithelial cells is poorly understood. Therefore, the possible involvement of PI3K in the regulation of cAMP- and cGMP-induced duodenal epithelial CFTR activation was investigated in the present study. Forskolin and 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP) markedly stimulated duodenal mucosal HCO(3)(-) secretion and short-circuit current (I(sc)) in CFTR wild-type mice, which was significantly inhibited by CFTR(inh)-172, a highly potent and specific CFTR inhibitor. Forskolin and 8-Br-cGMP failed to stimulate duodenal HCO(3)(-) secretion and I(sc) in CFTR knockout mice. Moreover, forskolin- and 8-Br-cGMP-stimulated duodenal HCO(3)(-) secretion and I(sc) were significantly reduced by wortmannin and LY294002, two selective PI3K inhibitors that are structurally and mechanistically different. Forskolin and 8-Br-cGMP induced CFTR phosphorylation and shifted CFTR proteins to the plasma membrane of duodenal epithelial cells, which were inhibited by wortmannin and LY294002. Forskolin and 8-Br-cGMP not only increased the activity of PI3K but also induced the phosphorylation of Akt, a signaling molecule downstream of PI3K, which were again inhibited by wortmannin and LY294002. Together, our results obtained from functional, biochemical, and morphological studies demonstrate that PI3K pathway plays an important role in the regulation of cAMP- and cGMP-induced duodenal epithelial CFTR channel activity and intracellular trafficking.AJP Cell Physiology 07/2009; 297(3):C503-15. · 3.54 Impact Factor
