Urinary trypsin inhibitor suppresses the production of interstitial procollagenase/proMMP-1 and prostromelysin 1/proMMP-3 in human uterine cervical fibroblasts and chorionic cells.
The mechanisms by which urinary trypsin inhibitor (UTI) prevents preterm premature rupture of fetal membrane and premature cervical ripening were investigated. We, therefore, examined the effects of UTI on the production of matrix metalloproteinases (MMPs) which closely participate in the breakdown of extracellular matrix in cultured human uterine cervical fibroblasts and human chorionic cells. UTI suppressed specifically the production of interstitial procollagenase/proMMP-1 and prostromelysin 1/proMMP-3 from both cells in a dose-dependent manner (0.32-1.28 microM). This suppression was accompanied by a decrease in steady-state levels of their mRNAs. These results indicate for the first time that UTI down-regulates the production of proMMP-1 and proMMP-3 accompanying with the decrease in the expression of their mRNAs, and therefore UTI actually participates in the maintenance of fetal membranes and/or uterine cervix by overall suppression of MMP production along with the known inhibitory actions towards serine proteinases.
Imada
K
K
Department of Biochemistry, Tokyo University of Pharmacy and Life Science, School of Pharmacy, Hachioji, Japan.
Ito
A
A
Kanayama
N
N
Terao
T
T
Mori
Y
Y
D015152:Blotting, Northern; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000166:cytology / Q000201:enzymology*; D002823:Chorion / Q000166:cytology / Q000201:enzymology*; D017364:Collagenases / Q000096:biosynthesis*; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D020781:Matrix Metalloproteinase 1; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects*; D014327:Trophoblasts / Q000166:cytology / Q000201:enzymology; D014361:Trypsin Inhibitors / Q000494:pharmacology*
D004792:Enzyme Precursors; D006023:Glycoproteins; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D014361:Trypsin Inhibitors; D017364:Collagenases; D008666:Metalloendopeptidases; C048047:prostromelysin; D020781:Matrix Metalloproteinase 1; C028665:urinastatin