Role of prostaglandins in intestinal epithelial restitution
stimulated by growth factors.
Zushi, Shinichiro, Yasuhisa Shinomura, Tatsuya Kiyohara, Takeshi
Minami, Masamitsu Sugimachi, Yoshihumi Higashimoto, Syuji Kanayama,
Yuji Matsuzawa.
Second Department of Internal Medicine, Osaka University Medical
School, 2-2, Yamadaoka, Suita 565, Japan
APStracts 2:0230G, 1995.
Mucosal integrity is re-established 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
-keto prostaglandin F1[alpha] release induced by FCS. Furthermore,
addition of a stable prostaglandin I2 analog, OP-41483, reversed the
slowing of epithelial restitution induced by piroxicam. These results
suggest that endogenous prostaglandins play an important role in
regulating intestinal epithelial restitution.
Received 17 July 1995; accepted in final form 4 November 1995.
APS Manuscript Number G291-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 November 95