Signalling of ERK1/2, P38MAPK and P90RSK in HIV-associated pre-eclampsia

Abstract

Due to their significance in trophoblast differentiation and survival, we evaluated the expression of the cell signalling molecules; Extracellular signal–regulated kinase 1/2 (ERK1/2), Mitogen Activated Protein Kinase 38 (MAPK38) and p90 ribosomal protein S6 kinase (p90 RSK) in buffy coat samples. Eighty pregnant women attending a large hospital in Durban, South Africa were assigned into normotensive and pre-eclamptic groups and further stratified by their HIV status. The degree of phosphorylation of the analytes was determined using the Bio-Plex ProTM Cell Signalling Immunoassay. There was a significantly lower protein concentration of the analytes in the pre-eclamptic versus the normotensive patients, irrespective of HIV status (p < .0001). Also, there was no significant difference in expression of ERK1/2 (p = .4369), p38MAPK (p = .4720) and p90 RSK (p = .0188), according to HIV status. This study demonstrates a down-regulation of ERK1/2, p38MAPK and p90RSK prosurvival markers in pre-eclampsia. This implicates the involvement of the MAPK pathway in the pathogenesis of preeclampsia. Activation of these pathways may prove useful in increasing the body of evidence on prevention of placenta dysfunction and apoptosis. Impact statement What is already known on this subject? Preeclampsia occurring in co-morbidity with HIV is a public health problem among pregnant, black South-African women. There have been conflicting theories regarding the predisposition to the development of preeclampsia as a result of compromised immune response due to HIV infection. In normal pregnancies, the MAPK pathway plays a significant role in molecular processes involved in the cells including survival and differentiation of the placental trophoblast. ERK1/2, p38MAPK and p90RSK are members of the MAPK family, which are pro-apoptotic. Inhibition in the signalling of MAPKs has been found to result in oxidative stress, a process which contributes to the defective trophoblast invasion seen in preeclampsia. What do the results of this study add? The results from this study showed that there is no relationship between HIV infection and an increased predisposition to the development of preeclampsia. In addition, this study highlights a downregulation in the expression of ERK1/2, p38 MAPK and p90RSK in preeclampsia. What are the implications of these findings for clinical practice and/or further research? These findings demonstrate the potential of these analytes as biomarkers for the diagnosis of preeclampsia. Also, this may serve as a framework for further research in the prevention of preeclampsia by elucidating more on the pathway.