Changes in matrix metalloproteinase 2 activities in amniochorions during premature rupture of membranes.
OBJECTIVE
Increased proteolytic activities of matrix metalloproteinases (MMPs) such as MMP-3 and MMP-9 are associated with premature rupture of membranes at term. However, it is unclear whether MMP-2 is involved in the premature rupture of membranes. In this study, to elucidate the role of MMP-2, we evaluated the activity of MMP-2 and also the expression of pro-MMP-2, membrane type 1 (MT1)-MMP and tissue inhibitor of metalloproteinase (TIMP)-1 in premature rupture of membranes.


METHODS
Amniochorions were prepared from 29 subjects with no labor (cesarean section; CS, n = 10), labor (normal delivery; ND, n = 10), and labor during premature rupture of membranes (PROM, n = 9). MMP-2 activity was spectrophotometrically assayed by measuring the digestion of an MMP-2-specific substrate. The levels of pro-MMP-2, MT1-MMP and TIMP-1 were determined by Western immunoblotting.


RESULTS
The activity of MMP-2 in PROM was significantly higher than that in CS and ND (P <.05). In addition, the levels of MT1-MMP, an activator of MMP-2, were higher in PROM than in CS and ND. In contrast, the level of TIMP-1, an inhibitor of MMP-2 was substantially lower in PROM than CS and ND. Moreover, the levels of pro-MMP-2 were increased more significantly in PROM and ND than in CS (P <.05).


CONCLUSIONS
Our results suggest that the increased expression of pro-MMP-2 and MT1-MMP and decreased expression of TIMP-1 may result in the increased activity of MMP-2, which is involved in the degradation of extracellular matrix (ECM) of fetal membrane, thereby inducing the premature rupture of membranes at term.
Ota
Atsuyuki
A
Departments of Obstetrics and Gynecology, Juntendo University School of Medicine, Tokyo, Japan. oota3017@yahoo.co.jp <oota3017@yahoo.co.jp>
Yonemoto
Hisashi
H
Someya
Akimasa
A
Itoh
Shigeru
S
Kinoshita
Katsuyuki
K
Nagaoka
Isao
I
D000650:Amnion / Q000378:metabolism; D002823:Chorion / Q000378:metabolism; D004792:Enzyme Precursors / Q000096:biosynthesis*; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D011247:Pregnancy; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis*
D004792:Enzyme Precursors; D019715:Tissue Inhibitor of Metalloproteinase-1; D020778:Matrix Metalloproteinase 2