Investigating the Relationship between Serum Level of s-Met (Soluble Hepatic Growth Factor Receptor) and Preeclampsia in the First and Second Trimesters of Pregnancy

Abstract

Introduction. Preeclampsia (PE) is an important cause of mortality and morbidity for mothers, fetuses, and the newborns. Placenta plays a pivotal role in pathogenesis of PE. Hepatic growth factor (HGF) is a cytokine expressed by the mesenchymal stalk of placental villi during pregnancy and assumes a paracrine role in trophoblasts which express its receptor (c-MET). In the present study, we investigate the diagnostic value of s-Met (the soluble form of the receptor) in the first and second trimesters of pregnancy for early diagnosis of preeclampsia. Method and Materials. This is a case-control study conducted on 95 pregnant women. The serum level of s-Met was measured in the first and second trimesters, and the participants were followed until delivery. 44 individuals with preeclampsia (the case group) and 51 individuals without preeclampsia (the control group) were evaluated. Results. Serum level of s-Met in preeclamptic participants was lower than that of the control group in both the first and the second trimesters (P < 0.0001). In addition, serum levels of s-Met were significantly lower during the first and second trimesters in patients with early, severe preeclampsia compared to those with late, mild preeclampsia (P < 0.0001). The sensitivity and specificity of s-Met in the first and second trimesters were, respectively, (83%, 94%) and (77%, 94%) for early preeclampsia and (88%, 92%) and (86%, 98%) for severe preeclampsia. Conclusion. Considering our findings, serum level of s-Met may be used as a predictive factor for early detection of preeclampsia. Further research is required to corroborate the functional and therapeutic value of s-Met in preeclampsia.

HGF/c-Met signaling regulates early differentiation of placental trophoblast cells

“…We analyzed the concentration of plasma sMet and found that plasma sMet peaked at E10.5 in most of the CD1 pregnant mice. Consistently, plasma sMet levels also peak during mid-term pregnancy in normal pregnant women [20,21]. To some extent, our data suggest that HGF/c-Met signaling regulates placental cell functions in humans and mice in a similar manner and that CD1 pregnant mice could be a suitable animal model to study the function of HGF/c-Met signaling (Table 1).…”

“…The concentration of plasma sMet peaked at E10.5 in the majority of CD1 mice sMet is the soluble form of c-Met, formed after metalloprotease hydrolysis, and it hinders HGF binding to c-Met to a certain extent [7]. Plasma sMet levels peak during the second trimester (21-26 weeks) in humans [20,21], but the dynamic change of plasma sMet in pregnant mice is unclear. ELISA was performed to analyze the dynamic changes in plasma sMet levels at different time points throughout pregnancy in CD1 mice.…”

Mechanisms of trophoblast migration, endometrial angiogenesis in preeclampsia: The role of decorin

“…85 These findings are consistent with the reports of reduced HGF production by the PE placentas 87 and reduced soluble Met (s-Met) in the blood of PE mothers. 88…”

Angiogenesis, Lymphangiogenesis, and the Immune Response in South African Preeclamptic Women Receiving HAART

“…The expansion of new lymphatic vessels from pre-existing ones, called lymphangiogenesis, is controlled mainly by growth factors, i.e., VEGFs such as VEGF-C and its ligand VEGFR-3, VEGF-D [53,54,55], and other factors, i.e., hypoxia-inducible factor 1-α (HIF-1α), the Tie/angiopoietin system, neuropilin-2, and integrin-α 9 [56,57,58,59,60,61]. However, until recently, there was a paucity of data on the lymphatic profile during pregnancy and in PE [62,63,64].…”

“…The aforementioned groups instead observed a stromal network immunostained with podoplanin. Lymphangiogenesis was observed at the decidua [68,69,70,71,72] and the uterine wall [64,73].…”