Localization of matrix metalloproteinases and tissue inhibitor of metalloproteinases-2 in normal human and rabbit stomachs.
OBJECTIVE
Matrix metalloproteinases (MMPs) are endopeptidases that degrade extracellular matrix and are involved in the pathogenesis of gastrointestinal ulcer and cancer along with tissue inhibitors of metalloproteinases (TIMPs). The purpose of this study is to examine their localization and functions in the normal stomach.


METHODS
We examined the localization of MMP-1, MMP-2, MMP-9 and TIMP-2 in normal human and rabbit stomachs by light- and electron-microscopic immunohistochemistry and Western blotting, and the enzymatic activities of MMP-2 and MMP-9 by gelatin zymography.


RESULTS
Immunohistochemistry revealed their localization in parietal cells, and surface and foveolar epithelial cells. Electron-microscopic immunohistochemistry of parietal cells showed immunolabeling of MMP-2 and TIMP-2 in the cisternae of the rough endoplasmic reticulum, and that of MMP-1 and MMP-9 in tubular structures in their cytoplasm. Western blotting revealed that the densities of MMP-2 and MMP-9 bands were higher for the fundic gland region than for the pyloric gland region. Gelatin zymography revealed that tissue extracts of the fundic gland region exhibited higher enzymatic activity of MMP-2 and MMP-9 than those of the pyloric gland region.


CONCLUSIONS
Normal rabbit and human stomachs contain MMP-1, MMP-2, MMP-9, and TIMP-2 and these are mainly localized in, and synthesized by parietal cells.
Tatsuguchi
A
A
Department of Pathology, Nippon Medical School, Tokyo, Japan. fukuda@nms.ac.jp
Fukuda
Y
Y
Ishizaki
M
M
Yamanaka
N
N
D000328:Adult; D000818:Animals; D015153:Blotting, Western; D017364:Collagenases / Q000032:analysis*; D005260:Female; D005347:Fibroblasts / Q000201:enzymology / Q000648:ultrastructure; D005780:Gelatin; D018093:Gelatinases / Q000032:analysis*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D020781:Matrix Metalloproteinase 1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000032:analysis*; D009130:Muscle, Smooth / Q000201:enzymology / Q000648:ultrastructure; D010295:Parietal Cells, Gastric / Q000201:enzymology / Q000648:ultrastructure; D011817:Rabbits; D013270:Stomach / Q000201:enzymology* / Q000648:ultrastructure; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis*
D019716:Tissue Inhibitor of Metalloproteinase-2; D005780:Gelatin; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1