The expression of mucins in placental development and its association with preeclampsia
Date Issued
2009
Date
2009
Author(s)
Shyu, Ming-Kwang
Abstract
Trophoblast invasion is crucial for the development of normal placentas. One of the primary placental defect in preeclampsia and partly intrauterine fetal growth restriction is shallow invasion of the extravillous trophoblast into the decidua, which leads to incomplete spiral artery remodeling and inadequate uteroplacental perfusion.ucins are highly glycosylated proteins expressed by epithelial cells of various organs. The membrane-bound mucins, which possess a single transmembrane domain and a highly conserved cytoplasmic tail, include MUC1, MUC3A, MUC4, MUC12, MUC13, MUC15, MUC16, MUC17, and MUC20. Among the known mucins, MUC1 is best studied and plays crucial roles in regulating many cellular properties, including cell proliferation, apoptosis, adhesion, and invasion. Although MUC1 has been found to be expressed by trophoblasts of various species, its expression in the human placenta throughout pregnancy and its potential role in trophoblast invasion remain unclear. MUC15 is a membrane-bound mucin and the mRNA of MUC15 has been detected by RT–PCR in various human tissues. So far, physiological functions of MUC15 have never been investigated. In the present study, we therefore investigated MUC1 and MUC15 expression in the human placenta and the effect on the invasion of trophoblast cells. UC15 mRNA in human tissues was analyzed by Northern blot. MUC1 and MUC15 mRNA and protein in human placenta were detected by real-time RT-PCR and Western blot, respectively. The distribution of MUC1 and MUC15 was revealed by immunohistochemistry. The effects of MUC1 and MUC15 on trophoblast invasion in vitro were analyzed by matrigel invasion assay in human choriocarcinoma JAR and/or JEG-3 cells. The results showed that MUC15 was expressed most highly in human placenta. Both MUC1 and MUC15 mRNA and protein increased with gestational age (P < 0.05, first versus third trimester). Immunohistochemistry showed that MUC1 and MUC15 protein was expressed by both cytotrophoblasts and syncytiotrophoblasts, especially at the apical membrane of syncytiotrophoblasts. In addition, MUC1 and MUC15 were found to be present in the glandular epithelium of the decidua. Overexpression of MUC15 substantially decreased matrigel invasionf JAR and/or JEG-3 cells, which was closely associated with an increase in mRNA expression of tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2. Knockdown of MUC15 with small interfering RNA significantly reversed these effects (P < 0.05). Interestingly, we found two populations of extravillous trophoblasts, MUC1-positive and MUC1-negative cells, in decidua. The numbers of MUC1-positive extravillous trophoblasts were increased during placental development. Furthermore, MUC1 overexpression significantly (P< 0.01) suppressed matrigel invasion of trophoblast-like JAR cells which was associated with a decrease in MMP9 activity assessed by gelatin zymography. Besides, MUC1 expression was significantly higher in the placenta of severe preeclampsia if compared with normal ones.t seems that differential expression of MUC1 and MUC15 in human placentas may play a critical role in the regulation of trophoblast invasion. They may play some role in the disease process of preeclampsia. The clinical implications and further suggestions for pathophysiology studies are discussed here.
Subjects
decidua
metalloproteinases
mucin
placenta
pregnancy
syncytiotrophoblast
trophoblast invasion
SDGs
File(s)![Thumbnail Image]()
Loading...
Name
ntu-98-D93421004-1.pdf
Size
23.32 KB
Format
Adobe PDF
Checksum
(MD5):464baa696c04a862f8bc9617329bd2a0