Matrix metalloproteinases 2 and 9 in indomethacin-induced rat gastric ulcer

The restoration of functional connective tissue is a major goal of the woun d healing process. The 72- and 92-kD gelatinases (MMP-2 and MM P-9) are ext racellular matrix metalloproteinases (MMPs), which are known to degrade typ e IV and V collagens and gelatin, and have a potential role in wound healin g. The spatial and temporal gelatinolytic activities of MMP-2 and MMP-9 wer e analyzed as a function of ulcer age, in homogenates of rat, indomethacin- induced, chronic gastric ulcers. The rats were sacrificed on 1, 3, 7, 12, 1 8, 24 and 28 days after subcutaneous indomethacin injections. Zymographic a nalyses revealed elevated activation of MMP-9 and latent and active MMP-2 i n gastric ulcers, when compared to gastric tissue from non-indomethacin-tre ated rats. The intact tissue and tissue from ulcerous lesions contained MMP -2. The highest activity of MMP-2 was found in 3 day gastric ulcers and ret urned to the control level by day 24. MMP-9 was not present in the intact t issue and the highest gelatinolytic activity of MMP-9 was also observed on the 3rd day after administration of indomethacin. The activity thereafter d ecreased and returned to the control level by day 24. In situ hybridization was used to evaluate which cells synthesize MMP-2 and MMP-9. MMP-2 was see n mostly in fibroblast-like cells in the submucosa and MMP-9 in macrophage- like cells in the mucosa on the margins of the ulcers. Thus, we conclude th at these two MMPs seem to have different functions during the gastric ulcer injury/healing process. MMP-2 may participate in the physiological turnove r of the gastric extracellular matrix, whereas MMP-9 may be important in th e early phase of gastric ulcer formation and also in the healing process. C opyright (C) 2000 S. Karger AG, Basel.