Secretion of matrix metalloproteinase-2, matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases into the intrauterine compartments during early pregnancy

Abstract

Matrix metalloproteinases (MMPs) are important enzymes in tissue remodelling, a key event for the development of the fetal membranes and placenta and establishing the feto-maternal interface during early pregnancy. This study has examined the secretion of the gelatinases, MMP-2 (72 kDa) and MMP-9 (92 kDa), and the endogenous tissue inhibitors of metalloproteinases (TIMPs) into extra-embryonic coelomic and amniotic fluids, the two principal intra-uterine compartments of the first trimester, and compared them to amniotic fluid collected later in gestation. In extra-embryonic coelomic fluid, gelatin zymography demonstrated that MMP-2 (72 kDa) was the predominant gelatinase, with some MMP-9 present. A broad range of TIMPs corresponding to TIMP-1 and TIMP-2, glycosylated and unglycosylated TIMP-3 and TIMP-4 was detected in this compartment by reverse zymography and immunoblot analyses. There was little gelatinase or TIMP activity in amniotic fluid in the first trimester. In amniotic fluid from the second trimester after fusion of the membranes obliterating the extra-embryonic coelom, and at term elective caesarean section, MMP-2 is the predominant gelatinase present, with a broad spectrum of TIMPs. These findings demonstrate that predominantly MMP-2 and also MMP-9, regulated by a range of TIMPs, are involved in intra-uterine tissue remodelling during the establishment of pregnancy.

Antifibrotic effects of a tissue inhibitor of metalloproteinase-1 antibody on established liver fibrosis in rats

“…TIMPs are associated with a variety of biological processes, including uterine reorganization during preg- nancy, 41 cell cycle-dependent association with the nucleus as a potential mediator of cell growth, 42 erythroid cell potentiation, 7 and anticancer activities, such as inhibiting tumor angiogenesis and metastasis. 7,8 In liver fibrosis, expression of TIMPs-1 and -2 increases 9 -11 ; activated HSCs are the source of this increase.…”

Leukocyte distribution in the equine endometrium as a response to acute induced endometritis

“…The presence of gelatinase MMPs -9 and -2 in uterine lavage fluid was investigated using gelatin substrate zymography as described previously (Riley et al 1999). Activities of tissue inhibitors of MMPs (TIMPs) in uterine lavage fluid were analysed by reverse zymography as described by Riley et al (1999).…”

“…Activities of tissue inhibitors of MMPs (TIMPs) in uterine lavage fluid were analysed by reverse zymography as described by Riley et al (1999). Statistical analyses were performed on relative densitometric values of MMP and TIMP bands using a paired ttest.…”

Weakening and Rupture of Human Fetal Membranes – Biochemistry and Biomechanics

“…Although the mechanism of FM rupture at term or with PPROM is not well understood, we believe that PPROM occurs due to an abnormal early activation of the processes that weaken FM at term. Supportive findings of this theory are the marked upregulation of MMPs, pro-inflammatory cytokines and chemokines in amniotic fluid and FM in PPROM and chorioamnionitis (Cox et al, 1997;Maymon et al, 1999;Thomakos et al, 2010;BryantGreenwood et al, 1995;Fortunato et al, 2003;Riley et al, 1999;Locksmith et al, 2001;Xu et al, 2002). TNF and IL-1 specifically have been shown to induce apoptosis, induce MMP 9 and increase PGE 2 production in chorioamnion and cultured primary amnion cells (R.M.…”