Pigment epitheliumderived factor inhibits proliferation, invasion and angiogenesis, and induces ferroptosis of extravillous trophoblasts by targeting Wntßcatenin/VEGF signaling in placenta accreta spectrum.
Mol Med Rep
; 29(5)2024 May.
Article
in En
| MEDLINE
| ID: mdl-38488028
ABSTRACT
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 proangiogenic and antiangiogenic factors. The pigment epitheliumderived 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. HTR8/SVneo cells were transfected to overexpress or knock down PEDF. Cell proliferation and invasion were assessed using Cell Counting Kit8, 5ethynyl2'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, Fe2+, 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 BML284 and overexpression of vascular endothelial growth factor (VEGF) reversed the PEDF overexpressioninduced suppression of cell proliferation, invasion and tube formation. PEDF overexpressioninduced 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 Wntßcatenin/VEGF signaling. The findings of the present study suggested a novel regulatory mechanism of the phenotypes of EVTs and PAS.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Placenta Accreta
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Serpins
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Eye Proteins
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Ferroptosis
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Nerve Growth Factors
Limits:
Female
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Humans
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Pregnancy
Language:
En
Journal:
Mol Med Rep
Year:
2024
Document type:
Article