GASTRIC-ULCER HEALING IN THE RAT - KINETICS AND LOCALIZATION OF DE-NOVO PROCOLLAGEN SYNTHESIS

Background and aims-To gain further insight into the role of the extra cellular matrix during healing of peptic ulcers, sequential changes of procollagen expression were studied over 30 days of ulcer healing. Ma terials and methods-Procollagens alpha 1 (I), alpha 1 (III), and alpha 1 (IV) RNA and their polypeptides were assessed in acetic acid induce d rat gastric ulcers by in situ hybridisation and immunohistochemistry . Results-Three days after ulcer induction, intense hybridisation sign als were obtained with all probes, with procollagen alpha 1 (I) showin g the highest transcript levels. Procollagen gene expression remained elevated up to day 15, but was reduced to initial low levels on day 30 . Immunohistochemical staining documented increased deposition of the three procollagen types parallel to their respective transcript levels , again with type I showing the earliest and the most prominent deposi ts. The highest procollagen transcript levels were found in the intact submucosa surrounding the ulcer margins, followed by the muscularis p ropria and the serosa, with the lamina propria exhibiting the lowest t ranscript levels. Conclusion-The procollagens studied are regulated di fferentially at the transcriptional and post-transcriptional levels. T he early onset and long duration of procollagen expression as well as the involvement of all layers of the gastric wall points to their cent ral structural and functional role in gastric ulcer healing.