Remodeling of extracellular matrix in gastric ulceration

The quality of ulcer repair remains crucial for the stability of the injure d tissue and for preventing recurrence. Therefore, we studied the temporo-s patial expression of the fibrillar and basement membrane collagens (types I , III, and TV), the collagenase MMP-2 as well as its inhibitor TIMP-1 befor e and after oral administration of basic fibroblast growth factor (b-FGF) o ver 30 days in acetic acid-induced rat gastric ulcers. The alterations and the exact location of the mRNA transcripts and their precipitated proteins were visualized by means of radioactive in situ hybridization and immunohis tochemistry. Our data show that hybridization signals of procollagen I coul d first be identified 2 hours after ulcer induction. After 12 hours the ulc er was established and the mRNA was enhanced at the ulcer margin. After 24- 48 hours the other procollagen transcripts were detected and all were furth er upregulated over the mesenchymal cells of all gastric layers up to 21 da ys, then declined at 30 days. In contrast, MMP-2 became prominent after 48 hours and up to 21 days. TIMP-1 was enhanced at 72 hours. After oral admini stration of b-FGF the transcriptional activity of the procollagens and MMP- 2 was not significantly altered, while ulcer diameter was significantly red uced. We conclude that the early onset and long duration of collagens' expr ession points to their central structural and functional role in gastric ul cer healing, MMP-2 seems to be involved in both active ulceration and ECM r emodeling. The timing of TIMP/MMP expression may be critical for proper res toration of gastric wall integrity. Microsc. Res. Tech. 53:396-408, 2001. ( C) 2001 Wiley-Liss, Inc.