The major thrust of the proposed work is to identify at cellular level the mechanisms by which surface and other epithelial cells of the stomach and duodenum are injured and are repaired in circumstances commonly encountered in daily life. Simultaneously, factors which affect such injuries, both favorably and adversely, will be evaluated. The circumstances which allow or facilitate recovery of a cell, or those which lead to necrosis or programmed cell death are of special interest. Finally, the process of rapid repair of superficial injuries (restitution) and conditions which influence this restitution of epithelial continuity will be examined in detail. The investigations will be directed toward the following: a) To further understanding of the process of rapid epithelial repair (restitution) with particular reference to the role of intracellular pH, growth factors, and the extracellular matrix. Specifically, the following will be tested: whether activation of the Na+/H+ antiporter is essential for cell migration (restitution) to occur; whether the effect of growth factors to facilitate restitution is mediated by stimulation of the Na+/H+ antiporter; and whether various components of extracellular matrix influence restitution by affecting the Na+/H+ antiporter. b) To define both morphologically and biochemically in gastric mucosal epithelial cells differences between necrotic cell death and programmed cell death. c) To evaluate the reversibility of gastric mucosal epithelial injury of the type encountered in daily living or as a result of an infection such as that caused by Helicobacter pylori and to investigate mechanisms of protection against such injuries.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK015681-28
Application #
6137962
Study Section
Surgery and Bioengineering Study Section (SB)
Program Officer
Hamilton, Frank A
Project Start
1977-01-01
Project End
2002-12-31
Budget Start
2000-01-01
Budget End
2000-12-31
Support Year
28
Fiscal Year
2000
Total Cost
$384,686
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02215
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Kang, Hye Won; Ribich, Scott; Kim, Brian W et al. (2009) Mice lacking Pctp /StarD2 exhibit increased adaptive thermogenesis and enlarged mitochondria in brown adipose tissue. J Lipid Res 50:2212-21
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Ragasa, Regina; Nakamura, Eiji; Marrone, Lisa et al. (2007) Isothiocyanate inhibits restitution and wound repair after injury in the stomach: ex vivo and in vitro studies. J Pharmacol Exp Ther 323:1-9
Hagen, Susan J; Morrison, Sarah W; Law, Christina S et al. (2004) Restitution of the bullfrog gastric mucosa is dependent on a DIDS-inhibitable pathway not related to HCO3- ion transport. Am J Physiol Gastrointest Liver Physiol 286:G596-605
Ayabe, Tokiyoshi; Satchell, Donald P; Pesendorfer, Patrizia et al. (2002) Activation of Paneth cell alpha-defensins in mouse small intestine. J Biol Chem 277:5219-28
Abdul-Ghaffar Al-Shaibani, Tarik A; Hagen, Susan J (2002) Regulation of acid secretion and paracellular permeability by F-actin in the bullfrog, Rana catesbeiana. Am J Physiol Gastrointest Liver Physiol 282:G519-26
Nakamura, Eiji; Hagen, Susan J (2002) Role of glutamine and arginase in protection against ammonia-induced cell death in gastric epithelial cells. Am J Physiol Gastrointest Liver Physiol 283:G1264-75

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