SERPINE2, an inhibitor of plasminogen activators, is highly expressed in the human endometrium during the secretory phas
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RESEARCH
Open Access
SERPINE2, an inhibitor of plasminogen activators, is highly expressed in the human endometrium during the secretory phase Robert Kuo-Kuang Lee1,2,3†, Chi-Chen Fan4,5†, Yuh-Ming Hwu1,2,6, Chung-Hao Lu1, Ming-Huei Lin2,6, Ying-Jie Chen2, Sheng-Hsiang Li1,6,7*
Abstract Background: SERPINE2, also known as protease nexin-1, belongs to the serine protease inhibitor (SERPIN) superfamily. It is one of the potent SERPINs that modulates the activity of plasminogen activators (PAs). PAs and their SERPIN inhibitors, such as SERPINB2 and SERPINE1, were expressed in the human endometrium and were implicated in implantation. However, expression data about SERPINE2 in the human endometrium is still unknown. Thus, we conducted an investigation to reveal the spatiotemporal and cellular expression of SERPINE2 in the human uterus during the menstrual cycle. Methods: Seven patients who underwent a hysterectomy and samples of 120 archived patients’ endometrial curettage or parts of the uterus that were formalin-fixed and embedded in paraffin. Western blotting was performed to evaluate the specificity and sensitivity of the antibody. Immunohistochemistry was conducted to localize the SERPINE2 expression site. Quantitative analysis was conducted to evaluate expression levels of SERPINE2 in various sub-phases of the menstrual cycle. Results: The SERPINE2 protein was primarily detected in the uterine fluid during the mid- and late-secretory phases of the menstrual cycle. It was predominantly expressed in the luminal and glandular epithelium, less in the myometrium, and only dispersedly in certain stromal cells throughout the menstrual cycle. A quantitative analysis of expression levels of SERPINE2 in the glandular epithelium revealed that it was highly expressed in the endometrium during the secretory phase compared to the proliferative phase. Conclusions: The SERPINE2 protein is highly expressed in the endometrium during the secretory phase, indicating that it may participate in tissue remodeling involved in implantation.
Background The plasminogen activator (PA) system refers to the PA and its cognate inhibitors [1]. The system includes two forms of PA, tissue-type (PLAT or tPA) and urokinasetype (PLAU or uPA), and four forms of serine protease inhibitors (SERPIN), including SERPINA5 (also called protein C inhibitor, PCI), SERPINB2 (also called plasminogen activator inhibitor 2, PAI-2), SERPINE1 (also called plasminogen activator inhibitor 1, PAI-1), and SERPINE2 (also called protease nexin-1, PN-1) [2]. * Correspondence: [email protected] † Contributed equally 1 Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan Full list of author information is available at the end of the article
The PA system is associated with many reproductive processes, including ovulation, embryogenesis, and embryo implantation in female reproductive tissues [1,3]. How SERPIN modulates the proteolytic activities of PLAT/PLAU in reproductive tissue remodeling is of great importance. Tissue remodeling requires a fine-
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