Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-3 are key regulators of extracellular matrix degradation by mouse embryos
| Autor: | E J, Whiteside, M M, Jackson, A C, Herington, D R, Edwards, M B, Harvey |
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| Rok vydání: | 2001 |
| Předmět: |
Tissue Inhibitor of Metalloproteinase-3
Oligonucleotides Matrix Metalloproteinase Inhibitors Oligonucleotides Antisense Embryo Mammalian Kidney Cell Line Extracellular Matrix Mice Blastocyst Matrix Metalloproteinase 9 Cricetinae Culture Media Conditioned Culture Techniques Animals Embryo Implantation Enzyme Inhibitors |
| Zdroj: | Biology of reproduction. 64(5) |
| ISSN: | 0006-3363 |
| Popis: | Embryo implantation in humans and rodents is a highly invasive yet tightly controlled process involving extracellular matrix (ECM) degradation. Matrix metalloproteinase 9 (MMP-9) has been implicated as the major facilitator of this ECM degradation. MMP-9 is expressed by the embryo's trophoblast cells, whereas tissue inhibitor of metalloproteinases 3 (TIMP-3) is expressed by the maternal uterine cells immediately adjacent to the trophoblast. We examined the functional roles of MMP-9 and TIMP-3 during in vitro ECM degradation by mouse embryos. Blastocysts were treated with either MMP-9 antisense or sense oligonucleotides and incubated on an ECM gel. The extent of ECM degradation exhibited by the blastocysts due to proteinase secretion was quantified. Embryos exposed to MMP-9 antisense oligonucleotides exhibited reduced ECM-degrading activity as compared with controls, and this reduced activity was correlated with the level of MMP-9 secreted by the embryos. The functional role of TIMP-3 was then examined by incubating blastocysts on an ECM gel that had been impregnated with various amounts of TIMP-3. In a dose-dependent manner, increases in TIMP-3 resulted in a reduction in ECM degradation and were correlated with diminished MMP-9 activity. These results provide important functional evidence that in vitro ECM degradation is regulated by embryo-derived MMP-9 and ECM-derived TIMP-3. |
| Databáze: | OpenAIRE |
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