Membrane and soluble endoglin role in cardiovascular and metabolic disorders related to metabolic syndrome

Vicen, Matej; Igreja, Ivone Cristina; Tripská, K.; Vitverová, Barbora; Najmanová, Iveta; Eissazadeh, Samira; Mičuda, Stanislav; Nachtigal, Petr

doi:10.1007/s00018-020-03701-w

Cited by 23 publications

(31 citation statements)

References 98 publications

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“…Subsequently, GO enrichment of DERNAs suggested that immune injury substantially linked endothelial dysfunction to PE and thus might affect intercellular signaling; KEGG enrichment revealed that the microbiome and metabolic disorders had a profound influence on endothelial dysfunction and PE. These findings were consistent with those of previous studies on the mechanism of endothelial dysfunction in PE (Ahmadian et al, 2020;Aneman et al, 2020;Aplin et al, 2020;Vicen et al, 2020). In addition, it was remarkable that several reported PE-associated pathways, including the "Wnt signaling pathway" (Schlosser et al, 2020), "Toll-like receptor signaling pathway" (He et al, 2018), "mTOR signaling pathway" (He et al, 2019), "p53 signaling pathway" (Gao et al, 2016), and "JAK-STAT signaling pathway" (Zhao and Jiang, 2018) were also depicted.…”

Section: Discussionsupporting

confidence: 90%

“…In addition, preeclampsia is regarded as a risk factor for longterm postpartum cardiovascular disease (CVD) (Benschop and Duvekot, 2019;Lane-Cordova et al, 2019). Growing evidence suggests that vascular endothelial dysfunction is critical for the pathogenesis of preeclampsia (Cubro et al, 2020;Mauro et al, 2020;Vicen et al, 2020). Immunological changes (Aneman et al, 2020), metabolic syndrome (Scioscia et al, 2015;Vicen et al, 2020), and endothelial dysfunction are intertwined in preeclampsia.…”

mentioning

confidence: 99%

“…Growing evidence suggests that vascular endothelial dysfunction is critical for the pathogenesis of preeclampsia (Cubro et al, 2020;Mauro et al, 2020;Vicen et al, 2020). Immunological changes (Aneman et al, 2020), metabolic syndrome (Scioscia et al, 2015;Vicen et al, 2020), and endothelial dysfunction are intertwined in preeclampsia. Nevertheless, the exact mechanism of endothelial dysfunction in preeclampsia still needs to be fully elucidated.…”

mentioning

confidence: 99%

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Identification of mRNA-, circRNA- and lncRNA- Associated ceRNA Networks and Potential Biomarkers for Preeclampsia From Umbilical Vein Endothelial Cells

Chen

Zheng

et al. 2021

Front. Mol. Biosci.

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ObjectiveThe etiology and pathogenesis of preeclampsia (PE) remain unclear, and ideal biomarkers for the early detection of PE are scarce. The involvement of the competing endogenous RNA (ceRNA) hypothesis in PE is only partially understood. The present study aimed to delineate a regulatory network in PE comprised of messenger RNAs (mRNAs), circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and microRNAs (miRNAs) via ceRNA profiles from human umbilical vein endothelial cells (HUVECs) to further reveal the pathogenesis of PE and potential biomarkers.MethodsDifferentially expressed mRNAs, circRNAs, and lncRNAs were detected in HUVECs from early onset preeclampsia (EOPE) cases (n = 4) and normal pregnancies (n = 4) by microarray analysis. Bioinformatics analysis was performed to systematically analyze the data, and a relevant ceRNA network was constructed. RNAs (ANGPT2, LIPG, hsa_circ_0025992, hsa_circ_0090396, hsa_circ_0066955, hsa_circ_0041203, hsa_circ_0018116, lnc-C17orf64-1:1, lnc-SLC27A2-2:1, and lnc-UEVLD-5:1) were validated by quantitative real-time PCR (qRT-PCR) in 10 pairs of HUVECs and placental tissues from PE patients and normal pregnancies. Furthermore, expression of hsa_circ_0025992 was detected in maternal peripheral blood samples from PE patients (n = 24) and normal pregnancies (n = 30) to confirm its potential as a novel biomarker. The receiver operating characteristic (ROC) curve was applied to analyze its diagnostic value.ResultsCompared with HUVECs from normal pregnancies, HUVECs from EOPE cases had 33 differentially expressed mRNAs (DEmRNAs), 272 DEcircRNAs, and 207 DElncRNAs. GO and KEGG analyses of the DERNAs revealed the biological processes and pathways involved in PE. Based on the microarray data and the predicted miRNAs, a ceRNA network was constructed with four mRNAs, 34 circRNAs, nine lncRNAs, and 99 miRNAs. GO and KEGG analyses of the network reinforced the crucial roles of metabolic disorders, the p53 and JAK/STAT signaling pathways in PE. In addition, ROC analysis indicated that hsa_circ_0025992 could be used as a novel biomarker for PE.ConclusionA novel ceRNA network was revealed in PE, and the potential of hsa_circ_0025992 to serve as a new biomarker was confirmed.

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Section: Discussionsupporting

confidence: 90%

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confidence: 99%

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confidence: 99%

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Identification of mRNA-, circRNA- and lncRNA- Associated ceRNA Networks and Potential Biomarkers for Preeclampsia From Umbilical Vein Endothelial Cells

Chen

Zheng

et al. 2021

Front. Mol. Biosci.

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“…Human endoglin is a type I integral membrane protein with a large (561 amino acids) glycosylated extracellular region, a single hydrophobic transmembrane domain, and a short cytosolic domain [ 1 ]. It is predominantly expressed on proliferating endothelial cells and plays a critical role in vascular pathophysiology [ 2 , 3 , 4 , 5 , 6 ]. In addition to the membrane-bound form, a soluble form of endoglin (sEng) can be generated by the action of the metalloproteases (MMP) MMP-14 or MMP-12 on the ectodomain of the membrane protein [ 7 , 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…In addition to the membrane-bound form, a soluble form of endoglin (sEng) can be generated by the action of the metalloproteases (MMP) MMP-14 or MMP-12 on the ectodomain of the membrane protein [ 7 , 8 , 9 , 10 ]. Abnormal levels of sEng were found in several endothelium-related pathological conditions, including preeclampsia [ 11 , 12 ], hypercholesterolemia and atherosclerosis [ 5 , 13 ], diabetes mellitus [ 14 ], hypertension [ 15 ], diabetic retinopathy [ 16 ], coronary artery disease [ 17 ], hereditary hemorrhagic telangiectasia [ 18 , 19 ], acute myocardial infarction [ 20 ] and cancer [ 21 , 22 ]. In some of these diseases, sEng has been postulated to be a biomarker for severity correlation and prognosis.…”

Section: Introductionmentioning

confidence: 99%

Generation of a Soluble Form of Human Endoglin Fused to Green Fluorescent Protein

Ruiz

Vega

Fernández

et al. 2021

IJMS

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Endoglin (Eng, CD105) is a type I membrane glycoprotein that functions in endothelial cells as an auxiliary receptor for transforming growth factor β (TGF-β)/bone morphogenetic protein (BMP) family members and as an integrin ligand, modulating the vascular pathophysiology. Besides the membrane-bound endoglin, there is a soluble form of endoglin (sEng) that can be generated by the action of the matrix metalloproteinase (MMP)-14 or -12 on the juxtamembrane region of its ectodomain. High levels of sEng have been reported in patients with preeclampsia, hypercholesterolemia, atherosclerosis and cancer. In addition, sEng is a marker of cardiovascular damage in patients with hypertension and diabetes, plays a pathogenic role in preeclampsia, and inhibits angiogenesis and tumor proliferation, migration, and invasion in cancer. However, the mechanisms of action of sEng have not yet been elucidated, and new tools and experimental approaches are necessary to advance in this field. To this end, we aimed to obtain a fluorescent form of sEng as a new tool for biological imaging. Thus, we cloned the extracellular domain of endoglin in the pEGFP-N1 plasmid to generate a fusion protein with green fluorescent protein (GFP), giving rise to pEGFP-N1/Eng.EC. The recombinant fusion protein was characterized by transient and stable transfections in CHO-K1 cells using fluorescence microscopy, SDS-PAGE, immunodetection, and ELISA techniques. Upon transfection with pEGFP-N1/Eng.EC, fluorescence was readily detected in cells, indicating that the GFP contained in the recombinant protein was properly folded into the cytosol. Furthermore, as evidenced by Western blot analysis, the secreted fusion protein yielded the expected molecular mass and displayed a specific fluorescent signal. The fusion protein was also able to bind to BMP9 and BMP10 in vitro. Therefore, the construct described here could be used as a tool for functional in vitro studies of the extracellular domain of endoglin.

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Correlation Between Endoglin and Malignant Phenotype in Human Melanoma Cells: Analysis of hsa-mir-214 and hsa-mir-370 in Cells and Their Extracellular Vesicles

Ruíz-Llorente

Ruiz-Rodríguez

Savini

et al. 2023

Advances in Experimental Medicine and Biology

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Endoglin (CD105) is an auxiliary receptor of transforming growth factor (TGF)-β family members that is expressed in human melanomas. It is heterogeneously expressed by primary and metastatic melanoma cells, and endoglin targeting as a therapeutic strategy for melanoma tumors is currently been explored. However, its involvement in tumor development and malignancy is not fully understood. Here, we find that endoglin expression correlates with malignancy of primary melanomas and cultured melanoma cell lines. Next, we have analyzed the effect of ectopic endoglin expression on two miRNAs (hsa-mir-214 and hsa-mir-370), both involved in melanoma tumor progression and endoglin regulation. We show that compared with control cells, overexpression of endoglin in the WM-164 melanoma cell line induces; (i) a significant increase of hsa-mir-214 levels in small extracellular vesicles (EVs) as well as an increased trend in cells; and (ii) significantly lower levels of hsa-mir-370 in the EVs fractions, whereas no significant differences were found in cells. As hsa-mir-214 and hsa-mir-370 are not just involved in melanoma tumor progression, but they can also target endoglin-expressing endothelial cells in the tumor vasculature, these results suggest a complex and differential regulatory mechanism involving the intracellular and extracellular signaling of hsa-mir-214 and hsa-mir-370 in melanoma development and progression.

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Membrane and soluble endoglin role in cardiovascular and metabolic disorders related to metabolic syndrome

Cited by 23 publications

References 98 publications

Identification of mRNA-, circRNA- and lncRNA- Associated ceRNA Networks and Potential Biomarkers for Preeclampsia From Umbilical Vein Endothelial Cells

Identification of mRNA-, circRNA- and lncRNA- Associated ceRNA Networks and Potential Biomarkers for Preeclampsia From Umbilical Vein Endothelial Cells

Generation of a Soluble Form of Human Endoglin Fused to Green Fluorescent Protein

Correlation Between Endoglin and Malignant Phenotype in Human Melanoma Cells: Analysis of hsa-mir-214 and hsa-mir-370 in Cells and Their Extracellular Vesicles

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