Proteinase-activated receptors in the endometrium and endometriosis

Yutaka Osuga
In: Frontiers in Bioscience · 2011 · vol. E4(1) , pp. 755 · doi:10.2741/416 · W4242253606
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PAR1 and PAR2 are expressed in endometrial and endometriotic cells and modulate distinct cellular responses, suggesting their potential as therapeutic targets for endometriosis.

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This review paper examines proteinase-activated receptors (PARs), focusing on PAR1 and PAR2, and their roles in the endometrium and in endometriotic lesions. It summarizes evidence that PAR1 and PAR2 are expressed in eutopic endometrial cells and in endometriotic cells, with thrombin and tryptase (typical activators of PAR1 and PAR2, respectively) produced in both endometrial tissue and endometriotic lesions. The paper reports that PAR1 activation in endometrial stromal cells increases vascular endothelial growth factor and matrix metalloproteinases while enhancing plasminogen activator activities, whereas PAR2 activation stimulates IL-8 and stem cell factor production and cell proliferation; in endometriotic stromal cells, PAR1 and PAR2 activation similarly drive cytokine/mediator production and proliferation (including IL-8, MCP-1, COX-2, IL-6, and IL-8). As a review, it does not present new experimental data and explicitly synthesizes prior findings to argue for PAR1 and PAR2 as possible therapeutic targets. This paper is centrally about endometriosis — it reviews PAR1/PAR2 expression and activation in endometriotic versus eutopic endometrial stromal cells and lesion-derived cells.

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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.
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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.

Keywords

- Endometrium - Endometriosis - Proteinase-Activated Receptor - Review

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