Growth factor regulation of the urokinase plasminogen activator (uPA) system in human endometrium, and the significance of uPA receptor activation in endometrial angiogenesis.

Research output: ThesisDoctoral Thesis (compilation)

Abstract

The purpose of this thesis was to examine the role of growth factors and the urokinase plasminogen activator (uPA) system in human endometrial angiogenesis. Growth factors as well as progesterone increased expression of the main inhibitor of uPA (PAI-1) in primary cultures of endometrial stromal cells. EGF, TGF-beta1 and bFGF increased gene transcription whereas progesterone increased mRNA stability. Although, both TGF-beta1 and progesterone increased expression of PAI-1, only TGF-beta1 increased uPA. As a consequence, extracellular concentration of uPA:PAI-1 complex was increased by TGF-beta1. The uPA:PAI-1 complex, as well as free uPA, increased migration of endothelial cells in a ”wound” assay. TGF-beta1 mRNA was increased in endometrial samples taken in mid/late secretory phase, but available evidence suggests that activation of latent TGF-beta by plasmin does not take place until the premenstrual rise in uPA activity, thus offering a potential pathway for paracrine stimulation of angiogenesis during endometrial regeneration. Endometrial tissue explants strongly stimulate endothelial cell migration. About 70 % of the chemotactic signal was blocked by antibodies to both the uPA receptor (uPAR) and EGF, separately or together. EGF stimulated the expression of uPAR as well as migration in EC, and this migration was blocked by antibodies to uPAR. These observations suggest that EGF is a major angiogenic signal in endometrial tissue, and that interaction with functional uPAR is required for the response.

Details

Authors
  • Tove Sandberg
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Obstetrics, Gynecology and Reproductive Medicine

Keywords

  • Obstetrics, endothelial cell migration, angiogenesis, uPA:PAI-1 complex, uPAR, TGF-beta, PAI-1, EGF, uPA, Growth factor, gynaecology, andrology, reproduction, sexuality, Obstetrik, gynekologi, andrologi, reproduktion, sexualitet
Original languageEnglish
QualificationDoctor
Awarding Institution
Supervisors/Assistant supervisor
  • [unknown], [unknown], Supervisor, External person
Award date2000 Dec 13
Publisher
  • Institutionen för Obstetrik och gynekologi, Universitetssjukhuset, 22185 Lund,
Print ISBNs91-628-4428-8
Publication statusPublished - 2000
Publication categoryResearch

Bibliographic note

Defence details Date: 2000-12-13 Time: 13:15 Place: Kvinnoklinikens föreläsningssal, Universitetssjukhuset, Lund External reviewer(s) Name: Ottesen, Bent Title: Professor Affiliation: Hvidovre Kvinnoklinik, Danmark ---