MMP-26 and TIMP-4 in the Human Endometrium

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.

Autorentext

Medical researcher;born in Uherske Hradiste,Czech Republic (CR); M.D.UJEP Brno,CZ,1989;Ph.D.Palacky University,Olomouc,CR,2001;Head Physician,Obst/Gyn,University Hospital, Olom.,CR,since 2004; Assoc.Prof.Pal.Univ.,Olom.,CR,2005;Ph.D.Lund Univ.,Sweden,2006;Deputy Dean study affairs, Pal.Univ.,Olom.,CR,since 2007; Married,Two children.

Klappentext
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.