Reduced angiogenic responses in adult endoglin heterozygous mice

Jerkić, Mirjana; Rodríguez-Barbero, Alicia; Prieto, Marta; Toporsian, Mourad; Pericacho, Miguel; Rivas-Elena, Juan V.; Obreo, Juana; Wang, Angela Yee-Moon; Pérez‐Barriocanal, Fernando; Arévalo, Miguel; Bernabéu, Carmelo; Letarte, Michelle; López‐Novoa, José M.

doi:10.1016/j.cardiores.2005.11.020

Cited by 113 publications

(129 citation statements)

References 22 publications

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“…Endoglin serves as an auxiliary receptor for TGF‐β signaling and is predominantly expressed in proliferating ECs and in tissues undergoing angiogenesis 37. Endoglin promotes ALK1‐mediated Smad1/5 signaling and inhibits ALK5‐mediated Smad2/3 signaling, leading to enhanced EC proliferation and angiogenesis 17, 18, 38, 39. Inhibiting endoglin expression by specific knockdown inhibits TGF‐β/ALK1 signaling and potentiates TGF‐β/ALK5 signaling,40, 41 resulting in reduced proliferation 19.…”

Section: Discussionmentioning

confidence: 99%

miR‐342‐5p Is a Notch Downstream Molecule and Regulates Multiple Angiogenic Pathways Including Notch, Vascular Endothelial Growth Factor and Transforming Growth Factor β Signaling

Yan

Cao

Liang

et al. 2016

JAHA

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BackgroundEndothelial cells (ECs) form blood vessels through angiogenesis that is regulated by coordination of vascular endothelial growth factor (VEGF), Notch, transforming growth factor β, and other signals, but the detailed molecular mechanisms remain unclear.Methods and ResultsSmall RNA sequencing initially identified miR‐342‐5p as a novel downstream molecule of Notch signaling in ECs. Reporter assay, quantitative reverse transcription polymerase chain reaction and Western blot analysis indicated that miR‐342‐5p targeted endoglin and modulated transforming growth factor β signaling by repressing SMAD1/5 phosphorylation in ECs. Transfection of miR‐342‐5p inhibited EC proliferation and lumen formation and reduced angiogenesis in vitro and in vivo, as assayed by using a fibrin beads–based sprouting assay, mouse aortic ring culture, and intravitreal injection of miR‐342‐5p agomir in P3 pups. Moreover, miR‐342‐5p promoted the migration of ECs, accompanied by reduced endothelial markers and increased mesenchymal markers, indicative of increased endothelial–mesenchymal transition. Transfection of endoglin at least partially reversed endothelial–mesenchymal transition induced by miR‐342‐5p. The expression of miR‐342‐5p was upregulated by transforming growth factor β, and inhibition of miR‐342‐5p attenuated the inhibitory effects of transforming growth factor β on lumen formation and sprouting by ECs. In addition, VEGF repressed miR‐342‐5p expression, and transfection of miR‐342‐5p repressed VEGFR2 and VEGFR3 expression and VEGF‐triggered Akt phosphorylation in ECs. miR‐342‐5p repressed angiogenesis in a laser‐induced choroidal neovascularization model in mice, highlighting its clinical potential.ConclusionsmiR‐342‐5p acts as a multifunctional angiogenic repressor mediating the effects and interaction among angiogenic pathways.

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Section: Discussionmentioning

confidence: 99%

miR‐342‐5p Is a Notch Downstream Molecule and Regulates Multiple Angiogenic Pathways Including Notch, Vascular Endothelial Growth Factor and Transforming Growth Factor β Signaling

Yan

Cao

Liang

et al. 2016

JAHA

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“…Suppression of endoglin gene expression using siRNA resulted in impaired TGF-β/ ALK1 signaling responses [49]. ECs derived from Eng-/-embryos were unable to proliferate in culture, displayed reduced migration, VEGF secretion and eNOS expression [49,52]. Interestingly, up-regulation of endoglin protects ECs from the apoptotic action of TGF-β1 [53].…”

Section: Role Of Tgf-β Signaling In Ecsmentioning

confidence: 99%

TGF-β signaling in vascular biology and dysfunction

2008

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Transforming growth factor (TGF)-β family members are multifunctional cytokines that elicit their effects on cells, including endothelial and mural cells, via specific type I and type II serine/threonine kinase receptors and intracellular Smad transcription factors. Knock-out mouse models for TGF-β family signaling pathway components have revealed their critical importance in proper yolk sac angiogenesis. Genetic studies in humans have linked mutations in these signaling components to specific cardiovascular syndromes such as hereditary hemorrhagic telangiectasia, primary pulmonary hypertension and Marfan syndrome. In this review, we present recent advances in our understanding of the role of TGF-β receptor signaling in vascular biology and disease, and discuss how this may be applied for therapy.

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“…Endoglin modulates endothelial-mesenchymal signaling and enhances cell proliferation [14]. Normal levels of endoglin are mandatory for physiologic angiogenic activity [27]. Endoglin knockout mice died of defective vascular development during early gestation [28].…”

Section: Discussionmentioning

confidence: 99%

Combined perioperative plasma endoglin and VEGF-A assessment in colorectal cancer patients.

Myśliwiec¹,

Pawlak²,

Kukliński³

et al. 2009

Folia Histochem Cytobiol.

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Abstract:Colorectal cancer growth and spread is absolutely dependent on angiogenesis with vascular endothelial growth factor (VEGF) being the most important cytokine involved in the process. Endoglin, a membrane co-receptor for TGF-β, has recently emerged as a sensitive index of cancer stage. There is now sufficient evidence indicating that microvessel density assessed by endoglin-immunostaining correlates with stage of colorectal cancer and patient survival. An association of a soluble form of endoglin with lymph node and distant metastases has recently been reported in two studies. Both of them used local elaborated immunoassays for endoglin assessment. The aim of our study was to determine the efficacy of plasma endoglin, assessed using a commercial kit, as a marker of tumor spread and distant metastases in colorectal cancer patients. We studied 48 colorectal cancer patients, compared with 22 healthy subjects, using ELISA. We observed that colorectal cancer patients had increased plasma VEGF-A, but not endoglin levels. However, we found an association of plasma endoglin with the stage of malignancy. Endoglin levels were increased in metastasis-positive patients when compared to both metastasis-negative patients and healthy volunteers. Plasma endoglin correlated with VEGF-A, CEA and CA19.9. Endoglin assessment in plasma does not seem useful as a maker of colorectal cancer. Our observations indicate however that it might be helpful in selecting patients with metastatic disease.

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Reduced angiogenic responses in adult endoglin heterozygous mice

Abstract: Although vascular development is normal in Eng(+/-) mice, angiogenic abnormalities were observed in the adult mice and their isolated endothelial cells. These results suggest that a normal level of endoglin is required for full angiogenic activity.

Cited by 113 publications

References 22 publications

miR‐342‐5p Is a Notch Downstream Molecule and Regulates Multiple Angiogenic Pathways Including Notch, Vascular Endothelial Growth Factor and Transforming Growth Factor β Signaling

miR‐342‐5p Is a Notch Downstream Molecule and Regulates Multiple Angiogenic Pathways Including Notch, Vascular Endothelial Growth Factor and Transforming Growth Factor β Signaling

TGF-β signaling in vascular biology and dysfunction

Combined perioperative plasma endoglin and VEGF-A assessment in colorectal cancer patients.

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