BACKGROUND: Matrix metalloproteinases (MMPs) and the plasminogen activator (PA)/ @entity1351 system are two major groups of proteases involved in the matrix degradation required for embryo implantation. We previously showed that the content of @entity4554 (CS) in @entity95 endometrium increases characteristically during the implantation period. Furthermore, CS has been reported to inhibit @entity563 proteases. In this study, we investigated whether CS can regulate the activity of proteases in cultured @entity1 endometrial stromal cells. METHODS AND RESULTS: CS (1-30 microM) and plasminogen (precursor of @entity1351 ) were added to the culture media of @entity1 endometrial stromal cells and incubated for 24 h. Culture media were collected for analysis of @entity1351 and @entity1476 enzyme activities using fluorescence assays. @entity1351 and @entity1549 activities were significantly reduced by CS in a dose-dependent manner (P < 0.001). Western blot analysis of the culture media revealed that CS inhibited the conversion by @entity1351 of @entity1549 from the precursor form to the active form. Fluorescence assay using a common substrate of @entity1476 and @entity1495 showed that enzymatic activity remains at approximately 50%, even at 30 microM CS. Gelatin zymography demonstrated that CS inhibited the activation of @entity1495 but not @entity1476 from the precursor, suggesting that the activation of @entity1476 may be independent of @entity1351 . CONCLUSIONS: CS inhibits not only @entity1351 activity but also MMP activities indirectly by inhibiting the @entity1351 -mediated process. These findings suggest that CS may be an important regulator of proteolysis during trophoblast invasion.

Inhibition of proteases involved in embryo implantation by XXXX .

@entity1 :: ('9606', 'Species') :: ['human'] @entity1476 :: ('4313', 'Gene') :: ['MMP-2, -3 and -9', 'MMP-2'] @entity95 :: ('9986', 'Species') :: ['rabbit'] @entity1549 :: ('4314', 'Gene') :: ['MMP-3'] @entity1351 :: ('5340', 'Gene') :: ['plasmin', 'Plasmin'] @entity1495 :: ('4318', 'Gene') :: ['MMP-9'] @entity563 :: ('CHEBI:17822', 'Chemical') :: ['serine'] @entity4554 :: ('MESH:C007045', 'Chemical') :: ['cholesterol sulfate']
@entity4554 :: (MESH:C007045,Chemical) :: ['cholesterol sulfate']
