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MMP-26 and TIMP-4 in the Human Endometrium
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The aim of this work was to study matrixmetalloproteinase-26 (MMP-26) and tissue inhibitorof metalloproteinases-4 (TIMP-4) in the humanendometrium. Both these enzymes may be implicated inthe implantation process. Trophoblast tissue fromhuman, as well as mice embryo produces pro-MMP-9.Active MMP-9 is a proteolytic enzyme with a broadsubstrate specificity. MMP-26 is an affectiveactivator of pro-MMP-9, and TIMP-4 is a stronginhibitor of MMP-26.We have shown that the endometrial expression of MMP-26 and TIMP-4 genes is maximal in mid-cycle. Theexpression pattern of both genes suggests their up-regulation by estrogen, and down-regulation byprogesterone. This is supported by our findings ofestrogen response elements upstream the codingsequences of both genes. Our findings suggest thatTIMP-4 is produced in the stroma only, and finallysecreted to the uterine fluid.Results of MMP-26 and TIMP-4 expression inhyperplastic tissue are in agreement with estrogenmediated regulation of these genes. MMP-26 and TIMP-4 expression in endometrial cancer decreases withthe loss of histological differentiation.
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