Levels Of Hepatocyte Growth Factor And Its Receptor (c-Met) In Pregnancies Complicated By Preeclampsia

BackgroundPreeclampsia is a human pregnancy-specific disorder that adversely affects the mother and the fetus. The incidence of preeclampsia is between 5% and 7% of pregnancies. Despite being one of the leading causes of maternal death and a major contributor to maternal and perinatal morbidity, the mechanisms responsible for the pathogenesis of preeclampsia remain unclear. It has been postulated that reduced placental perfusion may be an initiating event in preeclampsia, and most studies in humans suggested abnormal cytotrophoblast invasion of spiral arterioles is an important factor in leading to reduced placental perfusion. The mechanism for decreased trophoblast invasion in preeclampsia is unknown, abnormal trophoblast integrin expression, a number of cytokines, and hypoxia have all been implicated in this process.Hepatocyte growth factor (HGF) was first identified in 1984. It is synthesized and secreted by various organs such as liver, kidney, lung and placenta. The receptor for HGF was identified as a c-met proto-oncogene product, and was found to be a transmembrane protein. Intracellular signaling pathways driven by HGF-c-Met receptor coupling lead to multiple biological responses, including mitogenic,motogenic, morphogenic, angiogenic, and anti-apoptotic activities. In placenta during pregnancy, HGF was located in mesenchyme and c-Met receptor was mainly expressed in cytotrophoblast. Considerable evidence indicates that HGF has a number of important effects on extravillous trophoblasts such as promoting proliferation and differentiation, promoting invasion and inhibiting apoptosis. Abnormal expression of HGF and/or c-Met receptor is taken as an important etiologic factor in preeclampsia by causing trophoblasts dysfunction.ObjectiveUsing the methods of ELISA and semiquantitative reverse transcription polymerase chain reaction (RT-PCR), we were to observe the levels of HGF in maternal, fetal serum and placentas, and the expression levels of c-Met mRNA in placentas in preeclampsia.MethodsThe subjects are 33 patients who were diagnosed with preeclampsia during January 2004 through July 2005 from Shaoxing maternal and children's hospital. Among them, 15 patients were mild preeclampsia and the other 18 were severe preeclampsia. The controls were 32 term pregnant women during the same duration and had no undergoing diseases and complications including nephrosis liver disease and diabetes mellitus. Maternal anticubital vein blood samples and umbilical vein blood samples and placenta samples were collected. The ELISA method was used to detect the concentration of HGF in maternal and fetal serum and in placental tissue. The expression levels of HGF receptor (c-Met) mRNA in placentas were measured by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR).Results:Maternal serum HGF level decreased significantly in preeclampsia patientscompared with that in controls (PO.05). The level of fetal circulating HGF in preeclampsia group was at the same level as that of normal pregnancies (P>0.05). There was an extremely higher expression of placental HGF in preeclampsia patients than that in control group (PO.01). Whenever mild or severe preeclampsia, there seemed no significant difference in maternal, fetal and placental HGF between the two groups (P>0.05). HGF receptor, c-Met mRNA was expressed in placentas, but no difference was detected either between preeclampsia and control groups or between mild and severe preeclampsia subgroups (P>0.05).Conclusions:The decrease of maternal circulating HGF could be an important pathophysiologic change in preeclampsia, and may be one of the mechanisms of abnormal trophoblast invasion and shallow placentation. The measurement of serum HGF levels may add valuable information for diagnosing PE.The high placental HGF levels in PE may be resulted from the compensatory increasing synthesize from the ischemic placenta. The discrepancy of changes in circulating and placental HGF levels in preeclampsia indicates the extremely complex of pathogenesis of preeclampsia.No difference was found in expression of HGF receptor (c-Met) mRNA in placental tissue between preeclampsia and control groups, which indicates that HGF receptor level may not change at transcriptional level in the late trimester of pregnancy with preeclampsia.The level of HGF in fetal umbilical vein had no significance between preeclampsia and control groups, and it indicates that fetal circulating HGF may be uncorrelated with the disease of preeclampsia.