ISSN:
1573-2568
Keywords:
GASTRIC EPITHELIUM
;
EPITHELIAL INJURY
;
CELL PROLIFERATION
;
GROWTH FACTOR
;
SIGNAL TRANSDUCTION
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Immediate repair of the gastrointestinalepithelium after superficial injury is calledrestitution. It is based on the migration of thesurviving mucoid neck cells over the area of injury. Theinvolvement of growth factors in the process has beenrecently documented. They are known to enhance theprocess (ie, EGF, FGF, TGF-β) and to activate thebasolateral Na+-H+-antiport (EGF).They may exert their effect by activating intracellular tyrosinekinases or by inducing chemotaxis. Yet, their precisemechanism of action in the process is unknown. The aimof the present study was to investigate the effect of modulation of the signal transductionpathway on the occurrence of proliferative mucoid neckand foveolar cells in guinea pig gastric epithelium.Therefore guinea pig gastric epithelium was mounted in Ussing chambers in vitro and perfused 4 hrafter superficial injury with 1.25 M NaCl. The potentialdifference over the epithelium and tissue resistancewere recorded simultaneously. The tissue was exposed either to cycloheximide, genistein, or to4-phorbol myristate 13-acetate (PMA) during the 4-hrrecovery, and the expression of proliferative cells wasassessed by staining the tissue for proliferative cells (Ki-67). The mean proliferative index oftissues subjected to NaCl injury was significantlyhigher than that of uninjured control tissues after 4 hrof restitution. Inhibition of the signaling pathway with genistein decreased the proliferative indexsignificantly, while its stimulation with phorbolmyristate increased it. Both electrophysiologic andmorphologic restitution were sensitive to genistein, but not to PMA or cycloheximide. Superficialepithelial injury results in a significantly increasedoccurrence of proliferative cells in isolated guinea piggastric epithelium. This endogenous activation of the tissue is sensitive to inhibition bytyrosine kinases and to stimulation by protein kinases.Electrophysiologic and morphologic recovery are alsoaffected by the modulation of the signaling pathway. This suggests that it is involved in theimmediate repair process.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1018810830803
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