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The Production of Vascular Endothelial Growth Factor and Metalloproteinase via Protease-Activated Receptor in Human Endometrial Stromal Cells

The Production of Vascular Endothelial Growth Factor and Metalloproteinase via Protease-Activated Receptor in Human Endometrial Stromal Cells

Yuichi Furukawa, Yasushi Kawano, Junichiro Fukuda, Harunobu Matsumoto, Hisashi Narahara

Fertil Steril. 2009 Feb;91(2):535-41.

PMID: 18314110

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP141136836	Thrombin Receptor Activator Peptide 6		141136-83-6	Price

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