THE EXPRESSION OF PEPSINOGEN-C MESSENGER-RNA IN NORMAL GASTRODUODENALMUCOSA AND THE GASTRIC-ULCER MARGIN OF THE RAT

During the healing of experimental gastric ulcers in the oxyntic mucos a, there is a dedifferentiation of the glands in the ulcer margin: pre vious studies have shown that the parietal cells lose their capacity t o produce HCl, and mucous cells replace the zymogen cells. Primarily, we wished to investigate whether or not the glands of the ulcer margin transcribe mRNA for pepsinogen; secondly we also wanted to locate suc h transcription in other parts of the gastroduodenal epithelium. For t his purpose, we first established the baseline for distribution of pep sinogen mRNA in normal rats. We then studied its location in the margi n of ulcers in the corpus region after 1-15 days of healing. Formaldeh yde-fixed paraffin sections were used for in situ hybridization of mRN A for pepsinogen C, utilizing radioactive riboprobes. The normal gastr oduodenal mucosa showed widespread hybridization: the signal was parti cularly strong in the zymogen cells; weaker signals were obtained from the mucous neck cells, and the cells of the cardiac, antral, and Brun ner glands. Specific hybridization was weak or absent in the ulcer mar gin during the entire period studied. It is concluded that the capacit y to produce pepsinogen C is significantly reduced or absent in the ga stric ulcer margin during the first 15 days of healing; this should re duce the risks of peptic attack on the delicate scar and margin tissue s during ulcer healing.