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  • Title: miR-204-5p promotes preeclampsia serum-induced injury in human umbilical vein endothelial cells through regulation of the PTPRJ/Notch axis.
    Author: Liang X, Chen S, Wang X, Zhou L, Chen L.
    Journal: Pregnancy Hypertens; 2022 Jun; 28():100-108. PubMed ID: 35313225.
    Abstract:
    OBJECTIVES: Preeclampsia (PE) remains the leading cause of high morbidity and mortality in pregnancy. Injury of human umbilical vein endothelial cells (HUVECs) contributes to PE initiation. This study aims to analyze the molecular mechanism of PE-induced injury in HUVECs. METHODS: HUVECs were cultured with serum collected from PE patients and healthy pregnant women. PE-treated HUVECs were transfected with miR-204-5p inhibitor, si-protein tyrosine phosphatase receptor J (PTPRJ), and FLI-06 (Notch signaling pathway inhibitor). Cell viability, apoptosis, migration, and angiogenesis were determined using the cell counting kit-8 method, flow cytometry, wound healing assay, tube formation assay, and ELISA. The binding relationship between miR-204-5p and PTPRJ 3'UTR sequence was verified using dual-luciferase reporter assay. The expressions of miR-204-5p, PTPRJ, Notch, and HES1 were determined using qRT-PCR and Western blot analysis. RESULTS: miR-204-5p levels were higher in PE serum. PE-treated HUVECs showed elevated miR-204-5p expression and apoptosis and reduced migration, angiogenesis and VEGF level. miR-204-5p inhibition alleviated HUVEC injury and upregulated PTPRJ transcription. Silencing PTPRJ partly reversed the protecting role of miR-204-5p inhibition in HUVECs. PTPRJ downregulation or FLI-06 treatment limited the expressions of Notch and HES1 and blocked the activation of the Notch signaling pathway, consequently promoting HUVEC injury. CONCLUSIONS: miR-204-5p inhibited PTPRJ transcription and the activation of the Notch signaling pathway, thereby enhancing HUVEC injury.
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