Functional identification of a rare vascular endothelial growth factor a ( VEGFA ) variant associating with the nonsyndromic cleft lip with/without cleft palate

Abstract

Vascular endothelial growth factor A (VEGFA) is a crucial growth factor, which participates in multiple processes of human growth and development, such as angiogenesis and osteogenesis and is also necessary for development of palate. The purpose of this study was to investigate the effect of a rare VEGFA mutation (NM_001025366.2 773 T > C p.Val258Ala) on the cell functions and osteogenesis. Here, we found that the VEGFA mutation has adverse effects on the function of human embryonic palatal plate mesenchymal (HEPM) cells, and may affect the development of palate. The VEGFA mutation has adverse effects on promoting cell proliferation and migration and inhibiting apoptosis in HEPM and HEK-293 cells. In addition, the mutant VEGFA allele has a negative influence on osteogenesis. Taken together, the rare variant of the VEGFA gene had an adverse effect on cell functions and osteogenesis, which may impact the development of the palate. And these findings suggested that VEGFA mutation (c.773 T > C) may lead to nonsyndromic cleft lip with or without cleft palate and also provide a new insight into the mechanism of VEGFA gene in osteogenesis and palatogenesis.

DeepFace: Deep-learning-based framework to contextualize orofacial-cleft-related variants during human embryonic craniofacial development

“…Additionally, genes from the vascular endothelial growth factor (VEGF) family have been observed in the mesenchyme surrounding Meckel’s cartilage. 52 Furthermore, rare variants in the VEGFA gene have been associated with nonsyndromic CL/P, 53 underscoring the significant role of endothelial cells in craniofacial development. In addition, our enrichment analyses identified epithelial cells and stromal cells (mesenchymal cells), both well documented for their involvement in OFC disorders, 54 as top related cell types.…”

MicroRNAs in Small Extracellular Vesicles from Amniotic Fluid and Maternal Plasma Associated with Fetal Palate Development in Mice

“…The endothelial cell migration and chemotaxis might play important roles in transporting macrophages to dead phagocytosed MEE cells. In addition, a previous study has confirmed that vascular endothelial growth factor A (VEGFA) plays an important role in palate osteogenesis [50]. This suggests that the ASVs involved in endothelial cell migration and chemotaxis might also regulate the initial osteogenesis during this stage.…”

miR-877-3p inhibits tumor growth and angiogenesis of osteosarcoma through fibroblast growth factor 2 signaling

“…Several regulatory factors have been recognized as stimulators of angiogenesis including activate hypoxia inducible factor (HIF-1α), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and platelet derived growth factor (PDGF) [ 29 ]. One the other hand, a number of growth factors have showed direct or indirect interaction with miR-877-3p.…”