Proteinase-activated receptors in the endometrium and endometriosis.
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.
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. yutakaos-tky@umin.ac.jp
Yutaka
Y
Osuga
Yasushi
Y
Hirota
Osamu
O
Yoshino
Tetsuya
T
Hirata
Kaori
K
Koga
Yuji
Y
Taketani
D000818:Animals; D004715:Endometriosis / Q000378:metabolism*; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D006801:Humans; D044463:Receptor, PAR-1 / Q000378:metabolism* / Q000502:physiology; D044464:Receptor, PAR-2 / Q000378:metabolism* / Q000502:physiology
D044463:Receptor, PAR-1; D044464:Receptor, PAR-2