AJP - Gastrointestinal and Liver Physiology, Vol 270, Issue 5 757-G762, Copyright © 1996 by American Physiological Society

ARTICLES

Role of prostaglandins in intestinal epithelial restitution stimulated by growth factors

S. Zushi, Y. Shinomura, T. Kiyohara, T. Minami, M. Sugimachi, Y. Higashimoto, S. Kanayama and Y. Matsuzawa
Second Department of Internal Medicine, Osaka University Medical School, Suita, Japan.

Mucosal integrity is reestablished after superficial injuries by a rapid resealing process, termed epithelial restitution, that is regulated by several growth factors and cytokines. Growth factors are also known to stimulate the synthesis of endogenous prostaglandins that mediate important functions in intestinal epithelial cells. Therefore, we examined the effect of endogenous eicosanoid production modulators, piroxicam, dexamethasone, and nordihydroguaiaretic acid (NDGA) on intestinal epithelial restitution using two cultured cell wound-resealing models, IEC-6 and Caco-2 cells. Epidermal growth factor, transforming growth factor-beta, hepatocyte growth factor, and fetal calf serum (FCS) accelerated intestinal epithelial restitution, and piroxicam significantly suppressed these stimulatory effects. Dexamethasone mimicked the action of piroxicam. No additive effect of piroxicam and dexamethasone was observed. NDGA did not affect epithelial restitution. Piroxicam abolished the increase in 6-ketoprostaglandin F1 alpha (PGF1 alpha) release induced by FCS. Furthermore, addition of a stable PGI2 analogue, OP-41483 [5(E)-6,9-deoxa-6,9-methylene-15-cyclopentyl-16,17,18,19,20-pen tanor-PGI2], reversed the slowing of epithelial restitution induced by piroxicam. These results suggest that endogenous prostaglandins play an important role in regulating intestinal epithelial restitution.

This article has been cited by other articles:

				P. Rastogi, A. Rickard, N. Dorokhov, D. J. Klumpp, and J. McHowat Loss of prostaglandin E2 release from immortalized urothelial cells obtained from interstitial cystitis patient bladders Am J Physiol Renal Physiol, May 1, 2008; 294(5): F1129 - F1135. [Abstract] [Full Text] [PDF]

				J. L. Gookin, J. A. Galanko, A. T. Blikslager, and R. A. Argenzio PG-mediated closure of paracellular pathway and not restitution is the primary determinant of barrier recovery in acutely injured porcine ileum Am J Physiol Gastrointest Liver Physiol, November 1, 2003; 285(5): G967 - G979. [Abstract] [Full Text] [PDF]

				D. Little, R. A. Dean, K. M. Young, S. A. McKane, L. D. Martin, S. L. Jones, and A. T. Blikslager PI3K signaling is required for prostaglandin-induced mucosal recovery in ischemia-injured porcine ileum Am J Physiol Gastrointest Liver Physiol, January 1, 2003; 284(1): G46 - G56. [Abstract] [Full Text] [PDF]

				J. L. Gookin, J. M. Rhoads, and R. A. Argenzio Inducible nitric oxide synthase mediates early epithelial repair of porcine ileum Am J Physiol Gastrointest Liver Physiol, July 1, 2002; 283(1): G157 - G168. [Abstract] [Full Text] [PDF]

				A T Blikslager, D N Zimmel, K M Young, N B Campbell, D Little, and R A Argenzio Recovery of ischaemic injured porcine ileum: evidence for a contributory role of COX-1 and COX-2 Gut, May 1, 2002; 50(5): 615 - 623. [Abstract] [Full Text] [PDF]

				U. Savla, H. J. Appel, P. H. S. Sporn, and C. M. Waters Prostaglandin E2 regulates wound closure in airway epithelium Am J Physiol Lung Cell Mol Physiol, March 1, 2001; 280(3): L421 - L431. [Abstract] [Full Text] [PDF]

				D. J. Ruthig and K. A. Meckling-Gill Both (n-3) and (n-6) Fatty Acids Stimulate Wound Healing in the Rat Intestinal Epithelial Cell Line, IEC-6 J. Nutr., October 1, 1999; 129(10): 1791 - 1798. [Abstract] [Full Text]

				D. K. Podolsky V. Innate mechanisms of mucosal defense and repair: the best offense is a good defense Am J Physiol Gastrointest Liver Physiol, September 1, 1999; 277(3): G495 - G499. [Abstract] [Full Text] [PDF]

				A. T. Blikslager, M. C. Roberts, and R. A. Argenzio Prostaglandin-induced recovery of barrier function in porcine ileum is triggered by chloride secretion Am J Physiol Gastrointest Liver Physiol, January 1, 1999; 276(1): G28 - G36. [Abstract] [Full Text] [PDF]