Remodeling of extracellular matrix in gastric ulceration.
The quality of ulcer repair remains crucial for the stability of the injured tissue and for preventing recurrence. Therefore, we studied the temporo-spatial expression of the fibrillar and basement membrane collagens (types I, III, and IV), the collagenase MMP-2 as well as its inhibitor TIMP-1 before and after oral administration of basic fibroblast growth factor (b-FGF) over 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 immunohistochemistry. Our data show that hybridization signals of procollagen I could first be identified 2 hours after ulcer induction. After 12 hours the ulcer was established and the mRNA was enhanced at the ulcer margin. After 24-48 hours the other procollagen transcripts were detected and all were further upregulated over the mesenchymal cells of all gastric layers up to 21 days, 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 administration of b-FGF the transcriptional activity of the procollagens and MMP-2 was not significantly altered, while ulcer diameter was significantly reduced. We conclude that the early onset and long duration of collagens' expression points to their central structural and functional role in gastric ulcer healing. MMP-2 seems to be involved in both active ulceration and ECM remodeling. The timing of TIMP/MMP expression may be critical for proper restoration of gastric wall integrity.
Shahin
M
M
Department of Medicine B, University of Münster, Germany. manal.shahin@gmx.de
Konturek
J W
JW
Pohle
T
T
Schuppan
D
D
Herbst
H
H
Domschke
W
W
D000818:Animals; D005109:Extracellular Matrix / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000235:genetics*; D011347:Procollagen / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis / Q000235:genetics*
D011347:Procollagen; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D016222:Fibroblast Growth Factor 2; D020778:Matrix Metalloproteinase 2