Differential localization and expression of urokinase plasminogen activator (uPA), its receptor (uPAR), and its inhibitor (PAI-1) mRNA and protein in endometrial tissue during the menstrual cycle

Abstract

Normal endometrium is a highly dynamic tissue, which responds to ovarian steroids with cyclic proliferation, differentiation (secretion), and degradation (menstruation). The urokinase plasminogen activator (uPA)-dependent proteolytic cascade as well as ligand activation of the uPA receptor (uPAR) is critically involved in physiological as well as pathophysiological aspects of tissue expansion and remodelling. Cyclic variation and distribution of uPA, uPAR and plasminogen activator inhibitor 1 (PAI-1) mRNA were examined by in situ hybridization, real-time PCR and northern blot in normal endometrium. Their corresponding proteins were localized with immunohistochemistry. uPA mRNA is exclusively expressed by stromal cells, whereas uPA protein is present in both epithelial and stromal cells. Immunostaining for uPA protein is reduced or undetectable at midcycle, thus coinciding with peak concentration of uPA in the uterine fluid. uPAR mRNA is expressed by epithelial cells in the proliferative phase and by stromal cells in the secretory phase. However, epithelial cells stain for uPAR protein throughout the cycle, suggesting that uPAR may detach from stromal cells and then bind to epithelial cells in the secretory phase. PAI-1 mRNA is located in vessel walls. The late secretory phase has greatly increased expression of all three mRNA and their proteins, mainly in pre-decidual cells in the superficial stroma. Discordant localization of the mRNA and proteins suggest that uPA is produced by stromal cells, released and bound to epithelial cells in both the proliferative and secretory phases, whereas uPAR is released from the stroma and bound to epithelial cells in the secretory phase. Also, the present data together with earlier reports suggest that uPA is released from the epithelial cells to the uterine fluid.

Two-Way Communication Between Endometrial Stromal Cells and Monocytes

“…13 The present DNA microarray data confirm differential expression of many genes that had been previously identified to be changed during decidualization. For example, prolactin 13 and PAI-1 20 have been shown to be increased in response to estrogen plus progesterone; our data confirm these findings. In contrast, E alone did not stimulate a phenotypic change in T-HESCs and few genes showed significant changes in expression in response to E alone.…”

Alterations in the endometrium of rats, rabbits, and Macaca mulatta that received an implantation of copper/low-density polyethylene nanocomposite

“…26,27 PAI-1 messengerRNA and protein are localized in endometrial epithelium and stromal cells around small blood vessels. 28 SP is thought to play important roles in the …”

Implantation of the Human Embryo: Research Lines and Models

“…The nature and the regulation of this receptivity in the human are unknown. This Swedish group has recently reported that urokinase plasminogen activator (uPA) mRNA is found in the endometrial stroma whereas uPA protein is located in both stromal and epithelial cells [6] . Similarly, in the secretory phase uPAR mRNA is found in the stroma and uPAR protein in the epithelium [6] .…”