Serum proteins differentially expressed in early- and late-onset preeclampsia assessed using iTRAQ proteomics and bioinformatics analyses

Abstract

Background Preeclampsia remains a serious disorder that puts at risk the lives of perinatal mothers and infants worldwide. This study assessed potential pathogenic mechanisms underlying preeclampsia by investigating differentially expressed proteins (DEPs) in the serum of patients with early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE) compared with healthy pregnant women. Methods Blood samples were collected from four women with EOPE, four women with LOPE, and eight women with normal pregnancies, with four women providing control samples for each preeclampsia group. Serum proteins were identified by isobaric tags for relative and absolute quantitation combined with liquid chromatography–tandem mass spectrometry. Serum proteins with differences in their levels compared with control groups of at least 1.2 fold-changes and that were also statistically significantly different between the groups at P < 0.05 were further analyzed. Bioinformatics analyses, including gene ontology and Kyoto Encyclopedia of Genes and Genomes signaling pathway analyses, were used to determine the key proteins and signaling pathways associated with the development of PE and to determine those DEPs that differed between women with EOPE and those with LOPE. Key protein identified by mass spectrometry was verified by enzyme linked immunosorbent assay (ELISA). Results Compared with serum samples from healthy pregnant women, those from women with EOPE displayed 70 proteins that were differentially expressed with significance. Among them, 51 proteins were significantly upregulated and 19 proteins were significantly downregulated. In serum samples from women with LOPE, 24 DEPs were identified , with 10 proteins significantly upregulated and 14 proteins significantly downregulated compared with healthy pregnant women. Bioinformatics analyses indicated that DEPs in both the EOPE and LOPE groups were associated with abnormalities in the activation of the coagulation cascade and complement system as well as with lipid metabolism. In addition, 19 DEPs in the EOPE group were closely related to placental development or invasion of tumor cells. Downregulationof pregnancy-specific beta-1-glycoprotein 9 (PSG9) in the LOPE group was confirmed by ELISA. Conclusion The pathogenesis of EOPE and LOPE appeared to be associated with coagulation cascade activation, lipid metabolism, and complement activation. However, the pathogenesis of EOPE also involved processes associated with greater placental injury. This study provided several new proteins in the serum which may be valuable for clinical diagnosis of EOPE and LOPE, and offered potential mechanisms underpinning the development of these disorders.

Systematic proteomics analysis of lysine acetylation reveals critical features of placental proteins in pregnant women with preeclampsia

“…Consistent with previous studies, we found that the expression of F13A1 was significantly down‐regulated in PE placental tissues, demonstrating that F13A1 may participate in the physiopathology of PE. Previous studies used iTRAQ proteomics to assess serum and urine protein profiles in patients with PE, and found that DEPs in PE was involved in the complement system and coagulation cascades pathway 39,67 . In the present study, there were some novel discoveries that 15 DAPs in PE were involved in the complement and coagulation cascades pathway.…”

“…Previous studies used iTRAQ proteomics to assess serum and urine protein profiles in patients with PE, and found that DEPs in PE was involved in the complement system and coagulation cascades pathway. 39 , 67 In the present study, there were some novel discoveries that 15 DAPs in PE were involved in the complement and coagulation cascades pathway. We hypothesize that these DAPs may participate in the occurrence and development of PE by influencing the complement and coagulation cascades pathway, although no evidence has been reported to support or deny this hypothesis.…”

“…Little is known about the relationship between other pathways and PE. Studies have reported that the activation of complement system and coagulation cascades are closely related to the pathogenesis of PE 37–39 . To investigate whether Kac can participate in the progression of PE by affecting the complement and coagulation cascades, we further analysed DAPs in this pathway, of which 15 DAPs between PE and NC showed 21 Kac sites, including14 up‐regulated Kac sites and 7 down‐regulated Kac sites (Figure 6).…”

Circulating Placental Alkaline Phosphatase Expressing Exosomes in Maternal Blood Showed Temporal Regulation of Placental Genes

“…APOL3, a regulator of angiogenesis and endothelial tube formation, may act via ERK1/2, FAK, and Akt signaling (25). It may have a role in the early onset of preeclampsia (26).…”

Pregnancy-Specific Glycoprotein 9 Enhances Store-Operated Calcium Entry and Nitric Oxide Release in Human Umbilical Vein Endothelial Cells

“…Because the placenta is directly linked to the maternal circulation, abnormalities in the expression of placental factors in women with preeclampsia can be detected in maternal serum protein levels. In a previous study by our team, we identified differentially expressed proteins in blood samples derived from patients with preeclampsia by using isobaric tags for relative and absolute quantitation (iTRAQ) combined with high-performance liquid chromatography–tandem mass spectrometry (LC-MS/MS) [ 23 ]. Compared with those in healthy pregnant women, PSG9 levels were significantly decreased in blood samples collected from pregnant women with preeclampsia.…”