Background: Superficial epithelial injury is followed by restitution which is based on the migration of the surviving mucosal cells to restore the disturbed epithelial continuity. There is previous data that heat-shock (HS) preconditioning may be utilized to enhance the tissue tolerance to injury. Yet, there is little data about the effect of preconditioning on restitution.
Methods: Guinea pig gastric mucosae were mounted and perfused in Ussing chambers. After stabilization, a HS (42 degrees C, 30 min) and concomitant heat-shock protein (Hsp) production was induced. After stabilization and reaching the normothermia, a superficial injury (1.25 mol/l NaCl) was induced. Subsequently, the tissue was allowed to restitute for 3 h. In some sets of experiments, protein synthesis was inhibited either with quercetin or with cycloheximide. During the experiment, transmucosal electrophysiological resistance (R) of the tissue was recorded. After the experiment, the mucosa was prepared for morphologic analysis and for Western blot.
Results: HS did not affect mucosal tolerance to hyperosmolar injury, but inhibited significantly restitution after injury and upregulated Hsp70 as well. The levels of Hsp70 correlated inversely with recovery of R and histology. Quercetin and cycloheximide abolished this effect of HS, while quercetin did not completely abolish Hsp70 upregulation.
Conclusion: Hyperthermic preconditioning inhibits the restitution of gastrointestinal mucosa in correlation with Hsp70 levels. The inhibition of restitution is sensitive to blockades of de novo protein synthesis and of Hsp70 production.
Copyright 2002 S. Karger AG, Basel