Deregulation of c-Src tyrosine kinase and its downstream targets in pre-eclamptic placenta.

Aim: Pre-eclampsia is a serious pregnancy disorder characterized by the new onset of hypertension and proteinuria in the second trimester of pregnancy. The determination of a key signaling regulatory mechanism involved in placental functions is critical to understanding the pathogenesis of pre-eclampsia. The aim of this study was to examine the activity of c-Src and its downstream targets, extracellular signal-regulated kinase 1/2, p38 and Jun N-terminal kinase, as well as nuclear factor (NF)-ĸB in placental tissues collected from women with pre-eclampsia.

Methods: Ten pre-eclamptic (PE) placentas and 10 control placentas were used in this study. The Western blot method was performed to evaluate the c-Src/ mitogen activated protein kinase/NF-ĸB signaling pathway in each group.

Results: c-Src phosphorylation at Tyr-416, used as a measure of c-Src activity, was significantly decreased in PE placentas relative to the control. Reduced c-Src activity resulted in the suppression of extracellular signal-regulated kinase 1/2 phosphorylation and a significant reduction in the phosphorylation of p38 and Jun N-terminal kinase in PE placentas. Moreover, IĸBα phosphorylation was significantly elevated, while NF-ĸB phosphorylation was suppressed in PE placentas.

Conclusions: The c-Src/MAPK/NF-ĸB signaling pathway may contribute to the pathogenesis of pre-eclampsia.