A4. EGFL7 in placenta trophoblast and endothelial cells: implications in the pathogenesis of pre-eclampsia

Massimiani, Micol; Salvi, Silvia; Piccirilli, Diletta; Vecchione, Lucia; Moresi, Sascia; Ferrazzani, Sergio; Stuhlmann, Heidi; Campagnolo, Luisa

doi:10.1080/14767058.2016.1234765

Cited by 6 publications

(5 citation statements)

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“…The primary manifestations of preeclampsia include the shallow invasion of trophoblasts into the endometrium, cessation of vascular remodeling in the uterine spiral arteries and the decreased surface area and density of the villi. Patients with preeclampsia often exhibit disordered vascular remodeling ( 22 , 23 ). Placental hypoperfusion causes placental hypoxia, metabolism disorders, placental sourced toxicity, vascular endothelial injury and an imbalance of vasoactive substances, which can eventually lead to the development of preeclampsia ( 24 ).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have suggested that preeclampsia may be associated with decreased placental trophoblast invasion, ischemia and hypoxia, increased apoptosis, abnormal lipid metabolism and other placental dysfunctions during pregnancy ( 28 – 30 ). It has been reported that the extravillous trophoblasts serve an important role in the process of recoil in spiral arteries; the diminished invasion of extravillous trophoblast cells leads to abnormal vascular remodeling and shallow embryo implantation and ultimately, the development of preeclampsia ( 22 , 31 ).…”

Section: Discussionmentioning

confidence: 99%

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Effects of forkhead box protein M1 on trophoblast invasion and its role in preeclampsia development

Cui

et al. 2018

Exp Ther Med

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The present study aimed to investigate the expression of the forkhead box protein M1 (FOXM1) in the placenta of patients with preeclampsia, and its effect on trophoblasts. A total of 28 patients with preeclampsia and 30 patients without preeclampsia (controls) who underwent cesarean section and were admitted to the Affiliated Hospital of Qingdao University between June 2013 and September 2016 were enrolled in the present study. The expression of FOXM1 in placental tissues was examined by reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemistry. HTR8/SVneo cells were used to measure the in vitro expression of the vascular endothelial growth factor (VEGF). The results demonstrated that FOXM1 expression was downregulated in the placental tissues of patient with preeclampsia (P<0.05). Following the silencing of FOXM1 expression, the proliferation of HTR8/SVneo cells was suppressed. The results of flow cytometry demonstrated that proportion of HTR8/SVneo cells in the G0/G1 phase and the proportion of apoptotic cells increased. The expression of the apoptosis regulator BCL-2, as well as the expression of VEGF mRNA and protein expression were also downregulated following FOXM1 silencing. FOXM1 may therefore promote the development of preeclampsia via the VEGF signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effects of forkhead box protein M1 on trophoblast invasion and its role in preeclampsia development

Cui

et al. 2018

Exp Ther Med

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“…Another study by Massimiani et al (2016) has found that the expression of EGFL7 mRNA increases from well differentiated to less differentiated tumors, indicating that EGFL7 could be critical in promoting oncogenesis and angiogenesis in a more advanced metastatic phase. Interestingly, by using an in vivo HCC xenograft mouse model, it was shown that miR-126 could inhibit tumor proliferation and angiogenesis by suppressing EGFL7 expression, possibly via binding to the untranslated region (UTR) region of Egfl7 mRNA (Hu et al, 2016).…”

Section: Gastric Cancermentioning

confidence: 99%

“…Subsequently, various studies have characterized epidermal growth factor-like domain-containing protein 7 (EGFL7) as an angiogenic signaling molecule (Chim et al, 2015;Parker et al, 2004) and an important regulator of cell membrane receptors, including tumor-associated EGF receptor (EGFR) (Wu et al, 2009), endothelial integrin receptors (Nikolic et al, 2013), and endothelial Notch receptors (Nichol et al, 2010). In addition, EGFL7 regulates placental vascularization and embryonic development (Lacko et al, 2017) and has been implicated in the pathogenesis of pre-eclampsia by regulating placenta trophoblast cells via mitogen activated protein kinase (MAPK), phosphatidylinositol-3 kinase (PI3K), and Notch signaling pathways (Massimiani et al, 2016). EGFL7 also mediates thymogenesis via fms-related tyrosine kinase 3 signaling (Salama, Hattori, & Heissig, 2017) and hyperoxia-induced lung injury of newborn rats (Cui et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

EGFL7: Master regulator of cancer pathogenesis, angiogenesis and an emerging mediator of bone homeostasis

Hong

Kuek

Shi

et al. 2018

Journal Cellular Physiology

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Epidermal growth factor-like domain-containing protein 7 (EGFL7), a member of the epidermal growth factor (EGF)-like protein family, is a potent angiogenic factor expressed in many different cell types. EGFL7 plays a vital role in controlling vascular angiogenesis during embryogenesis, organogenesis, and maintaining skeletal homeostasis. It regulates cellular functions by mediating the main signaling pathways (Notch, integrin) and EGF receptor cascades. Accumulating evidence suggests that Egfl7 plays a crucial role in cancer biology by modulating tumor angiogenesis, metastasis, and invasion. Dysregulation of Egfl7 has been frequently found in several types of cancers, such as malignant glioma, colorectal carcinoma, oral and oesophageal cancers, gastric cancer, hepatocellular carcinoma, pancreatic cancer, breast cancer, lung cancer, osteosarcoma, and acute myeloid leukemia. In addition, altered expression of miR-126, a microRNA associated with Egfl7, was found to play an important role in oncogenesis. More recently, our study has shown that EGFL7 is expressed in both the osteoclast and osteoblast lineages and promotes endothelial cell activities via extracellular signal-regulated kinase (ERK), signal transducer and activator of transcription 3 (STAT3), and integrin signaling cascades, indicative of its angiogenic regulation in the bone microenvironment. Thus, understanding the role of EGFL7 may provide novel insights into the development of improved diagnostics and therapeutic treatment for cancers and skeletal pathological disorders, such as ischemic osteonecrosis and bone fracture healing.

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“…Therefore, it may be hypothesized that aberrant FOXM1 expression could induce changes in intracellular signal transduction, leading to trophoblastic dysfunction and PE. The main pathological feature of the placenta in PE patients is insufficient trophoblast invasion into the endometrium, with the depth only reaching the decidua layer (9). This in turn results in defective physiological 'vascular recasting' of the uterine spiral arterioles and a reduction in villi area and density (10).…”

Section: Introductionmentioning

confidence: 99%

microRNA‑21 regulates the proliferation of placental cells via FOXM1 in preeclampsia

et al. 2020

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The present study determined the expression of microRNA (miRNA or miR)-21 and forkhead box M1 (FOXM1) in placenta and blood samples from patients with preeclampsia (PE), and investigated the relationship between miR-21 and FOXM1. A total of 32 pregnant women with PE and 28 healthy pregnant women were included in the study as the experimental and control groups, respectively. Placental tissues and peripheral blood were collected from all subjects. ELISA was performed to measure the level of FOXM1 protein in the blood. HTR8/SVneo cells overexpressing miR-21 were established by transfection with agomiR-21. Reverse transcription-quantitative PCR was performed to measure the expression of FOXM1 mRNA and miR-21 in the placenta, blood and cells, and western blotting was used to evaluate FOXM1 protein expression in the placenta. An MTT assay was also performed to assess cell viability. In addition, a dual-luciferase reporter assay was used to investigate the direct interaction between FOXM1 and miR-21. The occurrence of PE was found to be associated with reduced FOXM1 mRNA levels, and elevated FOXM1 protein expression may serve a regulatory role that when attenuated leads to the occurrence of PE. Furthermore, miR-21 may serve a regulatory role in the pathology of PE by downregulating FOXM1 expression at the transcriptional level. In HTR8/SVneo cells, the overexpression of miR-21 reduced cell viability, possibly via the reduction of FOXM1 expression. The dual-luciferase assay indicated that miR-21 directly binds to the 3'-untranslated region of FOXM1 to regulate its expression. The present study demonstrated that the expression of FOXM1 mRNA and protein is downregulated, whereas the expression of miR-21 is upregulated in the placenta and blood samples of PE patients. In conclusion, miR-21 may regulate placental cell proliferation via its effects on FOXM1 to promote the occurrence and development of PE.

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A4. EGFL7 in placenta trophoblast and endothelial cells: implications in the pathogenesis of pre-eclampsia

Cited by 6 publications

References 0 publications

Effects of forkhead box protein M1 on trophoblast invasion and its role in preeclampsia development

Effects of forkhead box protein M1 on trophoblast invasion and its role in preeclampsia development

EGFL7: Master regulator of cancer pathogenesis, angiogenesis and an emerging mediator of bone homeostasis

microRNA‑21 regulates the proliferation of placental cells via FOXM1 in preeclampsia

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