[Frontiers in Bioscience E4, 755-767, January 1, 2012]

Proteinase-activated receptors in the endometrium and endometriosis

Yutaka Osuga1, Yasushi Hirota1, Osamu Yoshino1, Tetsuya Hirata1, Kaori Koga1, Yuji Taketani1

1Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

TABLE OF CONTENTS

1. Abstract
2. Proteinase activated receptors: overview
3. Proteinase activated receptors in the endometrium
3.1. Role of Proteinase activated receptor 1 in the endometrium
3.2. Role of Proteinase activated receptor 2 in the endometrium
4. Proteinase activated receptors in endometriosis
4.1. Role of Proteinase activated receptor 1 in endometriosis
4.2. Role of Proteinase activated receptor 2 in endometriosis
4.3. Proteinase activated receptor 2 in mouse model of endometriosis
5. Perspective
6. Acknowledgement
7. References

1. ABSTRACT

Proteinase-activated receptors (PARs) are G protein-coupled receptors activated by various proteinases. PARs play important roles in haemostasis, thrombosis, and inflammation. PAR1 and PAR2 are expressed in endometrial cells from the eutopic endometrium and endometriotic cells derived from endometriotic lesions. A typical activator of PAR1, thrombin, and a typical activator of PAR2, tryptase, are produced in the endometrium as well as endometriotic lesions. PAR1 activation in endometrial stromal cells induces production of vascular endothelial growth factor and matrix metalloproteinases, and increases activities of tissue-type and urokinase-type plasminogen activator. PAR2 activation in endometrial stromal cells stimulates interleukin (IL)-8 and stem cell factor production and proliferation of the cells. PAR1 activation in endometriotic stromal cells induces production of IL-8, monocyte chemotactic protein-1, and cyclooxygenase-2, and proliferation of the cells. PAR2 activation in endometriotic stromal cells increases secretion of IL-6 and IL-8, and the number of the cells. These findings indicate a wide range of function of PAR1 and PAR2 in the endometrium and endometriosis, and suggest PAR1 and PAR2 as possible therapeutic targets for endometriosis.