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Matrix metalloproteinase expression, regulation and localisation in mediating trophoblast invasion

Morgan, Maria (1998) Matrix metalloproteinase expression, regulation and localisation in mediating trophoblast invasion. PhD thesis, Dublin City University.

During early human pregnancy fetal trophoblasts rapidly invade the uterus. The extent and timing of this invasion is precisely regulated. A family of matrix degrading enzymes, called the matrix metalloproteinases (MMPs) have been implicated as major role players in this process. The aims of the research presented in this thesis were to (i) establish a model system using trophoblast continuous cell lines to examine the role of MMPs in trophoblast invasion; (ii) investigate the factors which regulate expression of MMPs during this invasive process; (iii) study the expression of MMPs in vivo and examine the role of MMPs in pre-eclampsia; and (iv) isolate and characterise an antibody fragment to MMP-9 using phage display technology. A model system using trophoblast continuous cell lines was established. These cell lines were characterised extensively with regard to a number of properties including cytokeratin and vimentin expression, hCG, hPL, invasive ability, MMP and TIMP production. Using this system two members of the MMP family, MMP-2 and MMP-9 were identified as important mediators of trophoblast invasion in vitro. The modulation of MMP expression in trophoblast cell lines by cytokines, ECM components, hormones and hypoxic conditions was investigated. Expression of the MMP-2 gene could not be modulated by any of the factors investigated in this study. MMP-9 expression was found to be regulated by certain cytokines and ECM components. In particular IL-l-P was found to upregulate MMP-9 expression at the mRNA and protein level, and to increase the invasive ability of the cells in vitro. A pilot scale study of 9 pre-eclamptic and 10 normal placental biopsies demonstrated no correlation of MMP expression with disease state. Immunohistochemistry demonstrated the expression of MMP-2, MMP-7 and MMP-3 protein in both normal and pre-eclamptic placental sections. Using a phage display library several clones producing soluble single chain antibody fragments to MMP-9 were isolated following four rounds of panning against MMP-9 protein, however the antibody fragments were found to have low binding affinities.
Item Type:Thesis (PhD)
Date of Award:1998
Supervisor(s):McDonnell, Susan
Uncontrolled Keywords:Trophoblast; Metalloproteinases
Subjects:Biological Sciences > Biotechnology
DCU Faculties and Centres:DCU Faculties and Schools > Faculty of Science and Health > School of Biotechnology
Use License:This item is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 License. View License
ID Code:19094
Deposited On:02 Sep 2013 13:00 by Celine Campbell . Last Modified 02 Sep 2013 13:00

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