The goal of this laboratory is to identify mechanisms of intestinal repair in order to facilitate recovery of injured intestine. Intestinal ischemial reperfusion injury is of particular interest because of its role in the equine colic syndrome, the principal killer of horses. A model of ischemia/ reperfusion injury will be developed in the pig. It is possible that the pig will provide a better model for the human and the horse, because of similar low levels of xanthine oxidase. The relative contribution of ischemia and reperfusion to intestinal injury will be determined. Ischemic injury appears to he more important in large animal species than reperfusion injury, as opposed to rodent models in which reperfusion injury is prominent. Because of a failure to block reperfusion injury in the horse, and the questionable relevance of rodent models of reperfusion injury to the human, the repair process will be characterized. The ability of glutamine (GLN) and growth factors to enhance proliferation will be investigated, and the mechanism by which GLN facilitates repair will he examined. Specifically, activation of Jun-nuclear kinase and Mitogen-activated kinase, enzymes critical for the induction of """"""""early- immediate"""""""" genes, will be assessed. These studies should provide basic information on mechanisms of epithelial proliferation and alternative therapeutic approaches to ischemic injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DK009400-02
Application #
2377714
Study Section
General Medicine A Subcommittee 2 (GMA)
Program Officer
Podskalny, Judith M,
Project Start
1997-02-08
Project End
Budget Start
1997-02-08
Budget End
1998-02-07
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
North Carolina State University Raleigh
Department
Anatomy/Cell Biology
Type
Schools of Veterinary Medicine
DUNS #
City
Raleigh
State
NC
Country
United States
Zip Code
27695
Blikslager, A T; Roberts, M C; Argenzio, R A (1999) Prostaglandin-induced recovery of barrier function in porcine ileum is triggered by chloride secretion. Am J Physiol 276:G28-36
Blikslager, A T; Rhoads, J M; Bristol, D G et al. (1999) Glutamine and transforming growth factor-alpha stimulate extracellular regulated kinases and enhance recovery of villous surface area in porcine ischemic-injured intestine. Surgery 125:186-94
Blikslager, A T; Roberts, M C; Gerard, M P et al. (1997) How important is intestinal reperfusion injury in horses? J Am Vet Med Assoc 211:1387-9
Blikslager, A T; Roberts, M C (1997) Mechanisms of intestinal mucosal repair. J Am Vet Med Assoc 211:1437-41
Blikslager, A T; Roberts, M C; Rhoads, J M et al. (1997) Prostaglandins I2 and E2 have a synergistic role in rescuing epithelial barrier function in porcine ileum. J Clin Invest 100:1928-33