학술논문
Pigment epithelium-derived factor inhibits proliferation, invasion and angiogenesis, and induces ferroptosis of extravillous trophoblasts by targeting Wnt-[beta]-catenin/VEGF signaling in placenta accreta spectrum
vascular endothelial growth factor
vascular endothelial growth factor
Document Type
Report
Author
Source
Molecular Medicine Reports. May 2024, Vol. 29 Issue 5
Subject
Language
English
ISSN
1791-2997
Abstract
Introduction Extravillous trophoblast cells (EVTs) are a group of cells that serve a critical role in reproduction and development, and are associated with obstetrical and gynecological diseases, such as placenta [...]
Placenta accreta spectrum (PAS) is one of the most dangerous complications in obstetrics, which can lead to severe postpartum bleeding and shock, and even necessitate uterine removal. The abnormal migration and invasion of extravillous trophoblast cells (EVTs) and enhanced neovascularization occurring in an uncontrolled manner in time and space are closely related to the abnormal expression of pro-angiogenic and anti-angiogenic factors. The pigment epithelium-derived factor (PEDF) is a multifunctional regulatory factor that participates in several important biological processes and is recognized as the most efficient inhibitor of angiogenesis. The present study aimed to explore the effects of PEDF on EVT phenotypes and the underlying mechanisms in PAS. HTR-8/SVneo cells were transfected to overexpress or knock down PEDF. Cell proliferation and invasion were assessed using Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine and Transwell assays. In vitro angiogenesis was analyzed using tube formation assays. The degree of ferroptosis was assessed by evaluating the levels of lipid reactive oxygen species, total iron, [Fe.sup.2+], malondialdehyde and reduced glutathione using commercial kits. The expression levels of biomarkers of ferroptosis, angiogenesis, cell proliferation and Wnt signaling were examined by western blotting. PEDF overexpression decreased the proliferation, invasion and angiogenesis, and induced ferroptosis of EVTs. Activation of Wnt signaling with BML-284 and overexpression of vascular endothelial growth factor (VEGF) reversed the PEDF overexpression-induced suppression of cell proliferation, invasion and tube formation. PEDF overexpression-induced ferroptosis was also decreased by Wnt agonist treatment and VEGF overexpression. It was predicted that PEDF suppressed the proliferation, invasion and angiogenesis, and increased ferroptosis in EVTs by decreasing Wnt-[beta]-catenin/VEGF signaling. The findings of the present study suggested a novel regulatory mechanism of the phenotypes of EVTs and PAS. Key words: extravillous trophoblasts, invasion, angiogenesis, ferroptosis, Wnt, [beta]-catenin, vascular epidermal growth factor
Placenta accreta spectrum (PAS) is one of the most dangerous complications in obstetrics, which can lead to severe postpartum bleeding and shock, and even necessitate uterine removal. The abnormal migration and invasion of extravillous trophoblast cells (EVTs) and enhanced neovascularization occurring in an uncontrolled manner in time and space are closely related to the abnormal expression of pro-angiogenic and anti-angiogenic factors. The pigment epithelium-derived factor (PEDF) is a multifunctional regulatory factor that participates in several important biological processes and is recognized as the most efficient inhibitor of angiogenesis. The present study aimed to explore the effects of PEDF on EVT phenotypes and the underlying mechanisms in PAS. HTR-8/SVneo cells were transfected to overexpress or knock down PEDF. Cell proliferation and invasion were assessed using Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine and Transwell assays. In vitro angiogenesis was analyzed using tube formation assays. The degree of ferroptosis was assessed by evaluating the levels of lipid reactive oxygen species, total iron, [Fe.sup.2+], malondialdehyde and reduced glutathione using commercial kits. The expression levels of biomarkers of ferroptosis, angiogenesis, cell proliferation and Wnt signaling were examined by western blotting. PEDF overexpression decreased the proliferation, invasion and angiogenesis, and induced ferroptosis of EVTs. Activation of Wnt signaling with BML-284 and overexpression of vascular endothelial growth factor (VEGF) reversed the PEDF overexpression-induced suppression of cell proliferation, invasion and tube formation. PEDF overexpression-induced ferroptosis was also decreased by Wnt agonist treatment and VEGF overexpression. It was predicted that PEDF suppressed the proliferation, invasion and angiogenesis, and increased ferroptosis in EVTs by decreasing Wnt-[beta]-catenin/VEGF signaling. The findings of the present study suggested a novel regulatory mechanism of the phenotypes of EVTs and PAS. Key words: extravillous trophoblasts, invasion, angiogenesis, ferroptosis, Wnt, [beta]-catenin, vascular epidermal growth factor