Appraisal of hepatocyte growth factor signal transduction in the duality of HIV associated pre-eclampsia.

Abstract

Hepatocyte Growth Factor (HGF) is a potent mitogen with a tyrosine kinase receptor (HGFR), which upon binding and activation functions to promote angiogenesis, tumorigenesis, cell growth, cell mortality and morphogenesis via the RAS/MAPK/ ERK, PI3K/ PKB/AKT and JAK/ STAT3 pathways. Both HGF and its receptor, HGFR play an essential role in human placentation and embryonic development during pregnancy. This study determines the concentration of HGF and HGFR in the synergy of HIV infection and pre-eclampsia (PE). A total sample size of n=80 (n=40 pre-eclamptic and n=40 normotensive) women was used. These were further stratified into HIV-positive and HIV-negative women. Analysis of the growth factors were performed via the Bio-Plex multiplex immunoassay method. The expression of serum HGF, based on pregnancy type irrespective of HIV status, was significantly downregulated in preeclamptic women vs normotensive women (p≤0.005). In contrast HGFR expression was similar between the latter groups (p≤0.4956). Based on HIV status, both HGF and HGFR expression showed no significant difference between HIV- positive and HIV-negative women, regardless of pregnancy type (p=0.4409; p=0.8869). There was a significant difference of HGF and HGFR across all study groups (p≤0.0001) with a moderate correlation between HGF and HGFR. This study demonstrates a downregulation of HGF expression in preeclampsia compared to normotensive pregnancies irrespective of HIV status. This decline impedes trophoblast cell survival and apoptosis via aberrant signalling pathways that contribute to defective trophoblast invasion in PE. The similarity of HGF and HGFR in HIV positive and negative groups emanates from the immune restorative effect of anti-retroviral usage.