The production of vascular endothelial growth factor and metalloproteinase via protease-activated receptor in human endometrial stromal cells
Received 1 June 2007; received in revised form 26 November 2007; accepted 26 November 2007. published online 04 March 2008.
Objective
To measure the levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) induced by thrombin in endometrial stromal cells (ESC).
Design
Evaluation of the effects of thrombin, thrombin receptor activator peptide 6 (TRAP-6), and d-phenylalanyl-1-propyl-l arginine chloromethyl ketone (PPACK) on the production of VEGF and MMPs by ESC.
Setting
Research laboratory at the Oita University Medical School.
Patient(s)
Eight endometrial specimens in the secretory phase.
Intervention(s)
ESC were incubated for 24 hours with thrombin, TRAP-6, and PPACK.
Main Outcome Measure(s)
The levels of VEGF, MMP-1, and active MMP-2 were measured by enzyme-linked immunosorbent assay (ELISA). The presence of protease-activated receptor-1 (PAR-1) and activation of mitogen-activated protein (MAP) kinase were detected by Western blot analysis.
Result(s)
Following stimulation by thrombin and TRP-6, the production of VEGF, MMP-1, and active MMP-2 statistically significantly increased; U0126 and PPACK statistically significantly suppressed the increases in the production of VEGF, MMP-1, and active MMP-2 induced by thrombin and TRAP-6. Activity by MAP kinase was induced by treatment with thrombin and TRAP-6 and was suppressed by PPACK.
Conclusion(s)
The results suggest that thrombin stimulates the production of VEGF and MMPs by a mechanism involving the MAP kinase system. The increases in VEGF and MMPs may contribute to neovascularization, which promotes the proliferation of endometrium and placentation.
Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Oita, Japan
Reprint requests: Yasushi Kawano, M.D., Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Oita, Japan (FAX: 81-97-586-6687).
Y.F. has nothing to disclose. Y.K. has nothing to disclose. J.F. has nothing to disclose. H.M. has nothing to disclose. H.N. has nothing to disclose.
Supported in part by a Grant-in-Aid (No. 15591766) for Specific Research from the Ministry of Education, Sports, Science, and Culture of Japan.
ABSTRACT