Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.660525
Title: Cyclooxygenase-2 and prostaglandins in human endometrial function
Author: Perchick, G. B.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2005
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Abstract:
The initial aim of the research presented in this thesis was to investigate the temporal expression and signalling of the prostaglandin E2 pathway in the normal human endometrium across the menstrual cycle. During the course of my PhD, numerous reports were published implicating cyclooxygenase-2 and its products in angiogenesis through the expression of angiogenic factors such as vascular endothelial growth factor, basic fibroblast growth factor and angiopoietins. To investigate the potential role of cyclooxygenase-2 in regulation of endometrial angiogenesis, cDNA array technology was employed to identify differentially expressed genes that may be involved in vascular function. Using this technique, a total of 81 genes were differentially regulated including cathepsin D. Cathepsin D mRNA and protein expression were elevated in the cyclooxygenase-2 antisense cells compared with the sense and wild type cells. Cathepsin D is known to proteolytically cleave plasminogen to the antiangiogenic factor angiostatin. Hence, we investigated the generation of angiostatin from plasminogen in conditioned media collected from cyclooxygenase-2 sense, cyclooxygenase-2 antisense and wild type cells. The cleavage of angiostatin from plasminogen was markedly enhanced in conditioned media from cyclooxygenase-2 antisense cells compared with cyclooxygenase-2 sense and wild type cells. Co-incubation of plasminogen with pepstatin A, a selective cathepsin D inhibitor, markedly reduced the cleavage of angiostatin from plasminogen thus further implicating cathepsin D in the differential angiostatin production by the cyclooxygenase-2 sense and antisense cell lines.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.660525  DOI: Not available
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