Expression Changes Of GADD45Α,P38 MAPK In Placenta In Patients With Pre-eclampsia And Its Clinical Significance

Objective: To study the expression of Gadd45αand p38 MAPK in placentas and the correlations of Gadd45αprotein and sera sFlt-1 and sEng in preeclampsia(PE). To explore the clinical significance of Gadd45αplay an role in the pathogenesis of preeclampsia. So as to provide some new clues for the treatment of preeclampsia.Methods: Fifty-four pregnant women who delivered from September 2009 to March 2010 in the First Affiliated Hospital of Chongqing Medical University were chosen as the subjects.They were classified into mild preeclampsia group (n=20),severe preeclampsia group (n=16) and the control group (normal pregnant women undergo elective term cesarean sections without labor and perinatal complications, n=18). Western blotting and immunohistochemistry were employed to determine the expression and localization of Gadd45αand p-p38 MAPK protein respectively;Gadd45αmRNA level was determined by semi-quantitive RT-PCR; The levels of sera sFlt-1 and sEng were measured by enzyme-linked immunosorbent assay (ELISA). Results: (1)Immunohistochemistry identified that the positive stained cells were mostly located in trophoblast cells in normotensive placentas, whereas in preeclamptic placentas Gadd45αprotein and p-p38 MAPK protein were detected in trophoblast and endothelial cells, as well as a few stromal cells at increased levels.(2)The mRNA levels of Gadd45αwas significantly elevated in mild and severe preeclampsia groups compared to the control group (P<0.05) , and Gadd45αmRNA level in severe group was significantly higher than that in mild group (P<0.05)(.3)The data of Western blotting revealed that the Gadd45αprotein levels in each group were 0.22±0.11,0.65±0.15,1.34±0.17, respectively, with significant differences between each group(P<0.05);The p-p38 MAPK protein levels in each group were 0.32±0.08,0.72±0.12,1.45±0.21, respectively, with significant differences between each group (P<0.05);p38 MAPK protein levels in the total groups were no difference(P>0.05).(4)Compared with the control group, sFlt-1 and sEng concentrations in maternal circulation were significantly increasing in the preeclampsia groups, and concentrations in severe group were significantly higher than those in mild group (P<0.05) . (5)There were positive correlations between Gadd45αprotein levels and the concentrations of serum sFlt-1, sEng in preeclampsia groups( r1 = 0.88,P<0.05;r2 =0.87,P<0.05).Conclusion: Upregulation of Gadd45αin preeclampsia placentas may play an important role in the pathogenesis of preeclampsia. It may induce the increased maternal sera levels of sFlt-l and sEng by activating p38 MAPK signaling pathway, leading to deficient cytotrophoblastic invasion and abnormal placental vascular reconstruction during the pregnancy.