Introduction of PIGF
Placental growth factor (PIGF) belongs to the vascular endothelial growth factor (VEGF) protein family, is primarily secreted by placental trophoblast cells. It plays a distinctive regulatory role in the functions of trophoblast and endothelial cells. During the formation of the placenta, PIGF holds a crucial position and exhibits close associations with various placental functions. With a three-dimensional structure comprising 149 amino acids, PIGF shares a remarkable similarity with VEGF-A, displaying 53% sequence identity. Discovered in 1991 by Dr. Maria Graziella Persico, PIGF is a secreted dimeric glycoprotein with a distinct cystine knot motif. Encoded by the human PIGF gene, PIGF can exist in multiple isoforms, with PIGF-1 and PIGF-2 considered the major ones. These isoforms vary in size, secretion properties, and binding affinities, contributing to their diverse physiological functions.
Related Products
Fig. 1 PIGF and VEGF hetero and homodimer protein structures (Ryan D. H., et al. 2018).
The Receptor of PIGF
PIGF can interact with cell surface-expressed VEGF receptor-1 (VEGFR-1), promoting its autophosphorylation. This, in turn, triggers biological effects through a cascade effect by activating signaling pathways. VEGFR-1 exists primarily in membrane-bound and soluble forms, with the soluble form having secretion properties and acting as an endogenous antagonist to block the activation of receptor tyrosine kinase.
The Function of PIGF
PIGF regulates the function of nourishing leaf cells and is influenced by the local microenvironment. Research indicates that PIGF's modulation of nourishing leaf cell function is primarily achieved through activating the stress-activated protein kinase (SAPK) signaling pathway, preventing apoptosis in these cells. PIGF also plays a crucial role in regulating endothelial cell proliferation and promoting angiogenesis. Studies report a dose and time-dependent vascular generation in rabbit corneas treated with different PIGF doses, an effect blocked by PIGF antibodies. Moreover, PIGF stimulates migration and proliferation of umbilical vein endothelial cells and microvascular endothelial cells in vitro.
Expression and Regulation of PIGF during Normal Pregnancy
In early pregnancy, PIGF mRNA expression is strong in syncytiotrophoblasts of chorionic villi, while in late pregnancy, PIGF mRNA expression is most abundant in the placental vascular endothelial membranes. PIGF is primarily synthesized by trophoblast cells, diffusing to endothelial cells to regulate their function, enhancing placental oxygen supply. PIGF secretion intensifies with the ongoing pregnancy, primarily due to a gradual decrease in oxygen pressure within the placenta.
PIGF and Pregnancy Complications
Gestational Diabetes Mellitus (GDM) during Pregnancy
A study investigated placental tissues from 20 pregnant women with gestational diabetes mellitus (GDM) and 20 normal pregnant women (control group). In comparison to the control group, GDM pregnant women exhibited significantly reduced apoptosis of trophoblast cells and weakened caspase-3 activity. PIGF expression in GDM placentas was notably higher. High-glucose cultivation induced increased apoptosis in HTR-8/SVneo trophoblast cells, which was significantly reversed by PIGF pretreatment. This suggests that elevated PIGF expression may contribute to reduced trophoblast cell apoptosis in GDM placentas.
Pregnancy-Induced Hypertension (PIH)
The occurrence of placental shallow implantation has been closely associated with pregnancy-induced hypertension (PIH), with lower PIGF expression being one contributing factor. PIGF in plasma serves as a monitoring indicator for placental growth during pregnancy, predicting gestational diabetes mellitus (GDM), pregnancy-induced hypertension, and preeclampsia. Studies revealed a significant decrease in serum PIGF levels in PIH patients, with PIGF levels correlating with the severity of hypertension. Early detection of PIGF in pregnancy is crucial for predicting and diagnosing PIH.
Predicting Preeclampsia
Vascular development is crucial for normal placental development, and abnormal angiogenesis is considered a major factor in the development of preeclampsia and intrauterine growth restriction. PIGF levels can distinguish placental-origin preeclampsia by detecting levels below 100 pg/ml around weeks 20-22 of pregnancy. Several studies corroborate that decreased PIGF levels, increased PAPPA levels, and abnormal uterine artery Doppler indices are associated with the early prediction of preeclampsia. Combining PIGF testing with other parameters enhances sensitivity and diagnostic accuracy.
In conclusion, PIGF, a member of the VEGF family expressed in the placenta, plays a crucial role in regulating trophoblast and endothelial cell functions. Aberrant PIGF secretion is closely related to pregnancy complications such as gestational diabetes, pregnancy-induced hypertension, and preeclampsia. Detecting maternal blood PIGF levels is a promising serum marker for predicting adverse pregnancy outcomes, aiding in the early identification, differentiation, and monitoring of complications during pregnancy.
References
- Ryan D. H., et al. Placental growth factor: A review of literature and future applications. Pregnancy Hypertension. 2018, 14: 260-264.
- Chau K., et al. Placental growth factor and pre-eclampsia. Journal of Human Hypertension. 2017, 31(12): 782-786.
.
