The Study On Expression Of EMMPRIN In Preeclampsia Placenta And The Regulation Of EMMPRIN On MMPs Secretion Of Trophoblasts

IntroductionHypertensive disorder complicating pregnancy is a special disease which occurs during pregnancy, and is a major cause of maternal and fetal morbidity and mortality. The pathological change of the disease is hyperkinesias of systemic small arteries, and main clinic representation is hypertension, edema and albu-minuria. The pathogenesis of hypertensive disorder complicating pregnancy is obscure. Outbreak of the disease involves a number organs . At present, it is well known that susceptibility of hypertensive disorder complicating pregnancy is increased by multi - gene inheritance background, and the balance of immunity between maternal and fetus is destroyed, inadequate cytotrophoblasts substitute of endothelial cell of uterine spiral arterioles cause remodeling obstacle, then placenta will be anoxic and ischemia, and a number of toxin is released to circulation and induce endothelial cell injured, hyperkinesias of systemic small arteries, and induce tissues and placenta impaired.Cytotrophoblast invasion occur in early pregnancy during development of placenta. Cytotrophoblasts invade into uterine by adhesion to deciduas, dissolution of extracellular matrix (ECM) and transplant. Invasion of cytotrophoblast is regulated by adhesive molecules, growth factors and matrix metalloproteinase (MMPs) , dissolution of ECM at marten - fetus interface is a main part in implantation, which deletes obstacles of invasion. Cytotrophoblast dissolute ECM of deciduas by secreting MMPs. MMPs take part in pregnancy, MMP - 2 is a main molecule of MMP at early pregnancy, MMP - 9 at mid - late pregnancy.A number of studies suggested that the expression of MMPs was decreased , which was relative to the grade of the disease. Inadequate secretion of MMPs would lead to invasive ability of cytotrophoblast decreased and inadequate vessels of placenta and affect blood perfusion. So it is recognized that decrease of the expression of MMPs is relative to outbreak and development of hypertensive disorder complicating pregnancy.Cytotrophoblasts are similar to invasive neoplasms, which suggest that they may have a similar invasive mechanism. Extracellular matrix metalloproteinase inducer ( EMMPRIN) is a trans - membrane protein, a member of immunoglob-ulin super - family, expresses in a variety of neoplasms and stimulate fibroblasts and neoplasms secret MMPs, which is a main part of invasion and metastasis of cancer.ObjectiveEMMPRIN is a regulator of MMPs, it has been poorly represented in literature about the expression pattern and regulation of MMPs of EMMPRIN. The purpose of the study is to explain the problem and the function of EMMPRIN in normal and pathological pregnancy.MethodsWe studied the patio - temporal expression of EMMPRIN in villi and placenta during normal pregnancy with immunohistochemistry. And we detected the expression of EMMPRIN in placenta of normal pregnancy and preeclampsia with immunohistochemistry and RT - PCR. Cytotrophoblasts were culutured in serum - free medium and we detected the expression of EMMPRIN. Using EMMPRIN antibody stimulated cytotrophoblasts; we detected the secretion of MMP -2,9 with gel zymography.ResultsThe expression of extracellular matrix metalloproteinase inducer is obvious, and appeared mainly on membrane of cytotrophoblast, syncytiotrophoblast,cyto-trophoblast column of the villi of Gestational Week 6 to 9, med - term and term placenta and extravillous cytotrophoblast of deciduas. of med - term and term placenta The expression reached peak level at Gestational Week 6 and gradually decreased from Week 7 and stabilized to a weak level at med - term and term placenta when the expression of extravillous cytotrophoblast of deciduas was increased .The expression of EMMPRIN mRNA was detected by RT - PCR in placenta from Gestational Week 24 to 40. The expression of EMMPRIN was distinctly deceased in placenta of preeclampsia contrast to normal at mRNA and protein, the difference is obvious.The expression of EMMPRIN was located in membrane and plasm of cyto-trophoblasts primarily cultured in serum - free medium. The secretion of MMP -2, 9 was significantly inhibited by respectively EMMPRIN antibody in a dose -time - dependent manner.ConclusionsIn sum, these results show the spatio - temporal expression of EMMPRIN in villi and placenta during normal pregnancy. For the first time, we reported that the expression of EMMPRIN in placenta of preeclampsia was lower than normal and EMMPRIN regulated the secretion of MMP - 2, 9 of cyotrophoblast. SO the decreased expression of EMMPRIN in placenta of preeclampsia may be an important mechanism in the etiology of preeclampsia.