The metabolic role of LncZBTB39-1:2 in the trophoblast mobility of preeclampsia

Abstract

Preeclampsia is characterized by new onset of hypertension and proteinuria after 20 weeks' gestation and is a leading cause of maternal and neonatal morbidity and mortality. The pathogenesis of preeclampsia is often associated with aberrant trophoblast function that leads to shallow placental implantation. However, the exact underlying mechanisms remain unclear. Placental LncZBTB39-1:2 expression level was investigated in 20 healthy placentae and 20 placentae with preeclampsia using qRT-PCR, and the metabolic profile of trophoblasts overexpressing LncZBTB39-1:2 in vitro was analysed using gas chromatography-mass spectrometry (GC–MS). In this study, we found that the expression of LncZBTB39-1:2 was significantly higher in preeclamptic placentae than in healthy placentae. Our metabolomics results have shown that tricarboxylic acid cycle intermediates and metabolites related to carbohydrate metabolism were decreased with the overexpression of LncZBTB39-1:2 in HTR8/SVneo cells. These findings were validated by detecting a lower level of intracellular ATP in HTR8/Vneo cells. Furthermore, the migration of HTR8/SVneo cells was compromised when cells were transfected with a plasmid encompassing LncZBTB39-1:2 overexpression. From these results, we conclude that abnormal levels of LncZBTB39-1:2 expression might lead to aberrant conditions in HTR-8/SVneo trophoblast cells. Aberrant conditions might be associated with dysregulated trophoblast migration and subsequent failure of uterine spiral artery remodelling, a pathogenesis recognised as a contributing factor in the aetiology of preeclampsia.

Long Noncoding RNA in Preeclampsia: Transcriptional Noise or Innovative Indicators?

“…At present, increasing numbers of investigations have suggested that the occurrence of PE is associated with the abnormal energy metabolism. The expression of lncZBTB39-1:2 in placenta has the potential of decreasing the trophoblast activity by means of impacting the energy regulation, which may promote the progress of PE [73].…”

The metabolic role of the CD73/adenosine signaling pathway in HTR-8/SVneo cells: A Double-Edged Sword?

“…Evidence suggests that preeclamptic placentas presented with mitochondrial dysfunction [ 44 ] and glycolytic inhibition [ 45 ]. It has been reported that cell migration demands a large amount of energy generated from mitochondria [ 46 ], and that dysfunction in aerobic respiration attenuated trophoblast migration [ 47 ]. Liang et al demonstrated that inhibition of aerobic glycolysis impaired EMT, migration and invasion of trophoblast [ 48 ].…”

Shallow Placentation: A Distinct Category of Placental Lesions

“…Abnormal placentation (invasion of spiral arteries by trophoblast) leads to maternal inflammatory response secondary to oxidative stress. 12,32 On molecular level, some authors stress the role of the inflammatory cytokines, endothelial dysfunction, imbalance between proangiogenic and antiangiogenic factors, 33 defective replacement of epithelial cadherin by vascular endothelial cadherin, decreased preimplantation factor (PIF) normally promoting trophoblast invasion, reducing oxidative stress and downregulating annexin A2 gene and protein levels in the endometrium, elevated circulating sFlt1 levels, or impaired ELABELA action normally stimulating the invasion and migration of trophoblastic cells through the activation of downstream Pl3K/AKT/mTOR pathway. [34][35][36][37] The placentas from high-risk pregnancies are notorious for the coexistence of various lesions and patterns of injury, socalled overlap lesions and patterns, 16 hypoxic, thrombotic, inflammatory, fetal vascular malperfusion, maternal vascular malperfusion, etc.…”

“…On molecular level, some authors stress the role of the inflammatory cytokines, endothelial dysfunction, imbalance between proangiogenic and antiangiogenic factors, 33 defective replacement of epithelial cadherin by vascular endothelial cadherin, decreased preimplantation factor (PIF) normally promoting trophoblast invasion, reducing oxidative stress and downregulating annexin A2 gene and protein levels in the endometrium, elevated circulating sFlt1 levels, or impaired ELABELA action normally stimulating the invasion and migration of trophoblastic cells through the activation of downstream Pl3K/AKT/mTOR pathway. 34 35 36 37…”