MMP-26 and TIMP-4 in the Human Endometrium

The aim of this work was to study matrix metalloproteinase-26 (MMP-26) and tissue inhibitor of metalloproteinases-4 (TIMP-4) in the human endometrium. Both these enzymes may be implicated in the implantation process. Trophoblast tissue from human, as well as mice embryo produces pro-MMP-9. Active MMP-9 is a proteolytic enzyme with a broad substrate specificity. MMP-26 is an affective activator of pro-MMP-9, and TIMP-4 is a strong inhibitor of MMP-26.We have shown that the endometrial expression of MMP-26 and TIMP-4 genes is maximal in mid-cycle. The expression pattern of both genes suggests their up-regulation by estrogen, and down-regulation by progesterone. This is supported by our findings of estrogen response elements upstream the coding sequences of both genes. Our findings suggest that TIMP-4 is produced in the stroma only, and finally secreted to the uterine fluid. Results of MMP-26 and TIMP-4 expression in hyperplastic tissue are in agreement with estrogen mediated regulation of these genes. MMP-26 and TIMP-4 expression in endometrial cancer decreases with the loss of histological differentiation.