Localization of matrix metalloproteinases and tissue inhibitor of metalloproteinases-2 in normal human and rabbit stomachs

Background/Aims: Matrix metalloproteinases (MMPs) are endopeptidases that d egrade extracellular matrix and are involved in the pathogenesis of gastroi ntestinal ulcer and cancer along with tissue inhibitors of metalloproteinas es (TIMPs). The purpose of this study is to examine their localization and functions in the normal stomach. Methods: We examined the localization of M MP-1, MMP-2, MMP-9 and TIMP-2 in normal human and rabbit stomachs by light- and electron-microscopic immunohistochemistry and Western blotting, and th e enzymatic activities of MMP-2 and MMP-9 by gelatin zymography. Results: I mmunohistochemistry revealed their localization in parietal cells, and surf ace and foveolar epithelial cells. Electron-microscopic immunohistochemistr y of parietal cells showed immunolabeling of MMP-2 and TIMP-2 in the cister nae of the rough endoplasmic reticulum, and that of MMP-1 and MMP-9 in tubu lar structures in their cytoplasm. Western blotting revealed that the densi ties 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 extra cts of the fundic gland region exhibited higher enzymatic activity of MMP-2 and MMP-9 than those of the pyloric gland region. Conclusion: Normal rabbi t and human stomachs contain MMP-1, MMP-2, MMP-9, and TIMP-2 and these are mainly localized in, and synthesized by parietal cells.