Spatiotemporal expression of the serine protease inhibitor, SERPINE2, in the mouse placenta and uterus during the estrous cycle, pregnancy, and lactation

Sheng-Hsiang Li,Schu-Rern Chern,Edmund I Tsuen Chen,Chung-Hao Lu

doi:10.1186/1477-7827-8-127

Abstract

BackgroundSERPINE2, also known as glia-derived nexin or protease nexin-1, belongs to the serine protease inhibitor (SERPIN) superfamily. It is one of the potent serpins that modulates the activity of the plasminogen activator (PA) and was implicated in tissue remodeling. In this study, we investigated the expression patterns of SERPINE2 in the mouse placenta and uterus during the estrous cycle, pregnancy, and lactation.MethodsSERPINE2 was purified from mouse seminal vesicle secretion using liquid chromatography (LC) and identified by LC/tandem mass spectrometry. The antiserum against the SERPINE2 protein was raised in rabbits. To reveal the uterine and placental expression of SERPINE2, tissues at various stages were collected for real-time PCR quantification, Western blotting, and immunohistochemical staining.ResultsSerpine2 mRNA was the major PA inhibitor in the placenta and uterus during the estrous cycle, pregnancy, and lactation, although Serpine1 mRNA had higher expression levels than Serpine2 mRNA in the placenta. Plat seemed to be the major PA in the mouse uterus and placenta. Antiserum against the SERPINE2 protein specifically recognized two forms of SERPINE2 and an extra 75-kDa protein, which was probably a complex of SERPINE2 with a certain protease, from among thousands of protein components in the tissue extract as demonstrated by Western blotting. In the uterus, SERPINE2 was primarily localized in luminal and glandular epithelial cells but it also was detected in circular and longitudinal smooth muscle cells during the estrous cycle and lactation. It was prominently expressed in decidual stroma cells, the metrial gland, and endometrial epithelium of the pregnant uterus. In the placenta, SERPINE2 was expressed in trophoblasts of the labyrinth and spongiotrophoblasts. However, its expression was remarkably reduced in giant cells which existed in the giant cell-decidual junction zone. In contrast, prominent expression of SERPINE2 seemed to be detected on clusters of glycogen cells near the junction zone. In addition, yolk sac membranes also showed high expression of SERPINE2.ConclusionsThese findings indicate that SERPINE2 is a major PA inhibitor in the placenta and uterus during the estrous cycle, pregnancy, and lactation. It may participate in the PA-modulated tissue remodeling process in the mouse placenta and uterus.

Highlights

SERPINE2, known as glia-derived nexin or protease nexin-1, belongs to the serine protease inhibitor (SERPIN) superfamily
The activity of plasminogen activator (PA) is modulated by several protease inhibitors that belong to the serine protease inhibitor (SERPIN) superfamily, such as SERPINA5, SERPINB2, SERPINE1, and SERPINE2 [2]
Two forms, about 40- and 42-kDa bands, of SERPINE2 were detected from thousands of protein components in the uterine tissue extract collected from different phase of estrous cycle (Figure 1B, arrows)

Summary

Introduction

SERPINE2, known as glia-derived nexin or protease nexin-1, belongs to the serine protease inhibitor (SERPIN) superfamily. It is one of the potent serpins that modulates the activity of the plasminogen activator (PA) and was implicated in tissue remodeling. The mammalian uterus undergoes drastic tissue remodeling during the estrous cycle, implantation, and pregnancy. The plasminogen activator (PA) system refers to the PA and its cognate inhibitors [1]. The PA is involved in tissue remodeling by converting abundant extracellular plasminogen into plasmin, an active protease, which degrades the extracellular matrix. The activity of PA is modulated by several protease inhibitors that belong to the serine protease inhibitor (SERPIN) superfamily, such as SERPINA5, SERPINB2, SERPINE1, and SERPINE2 [2]

Methods

Results

Conclusion