Reducing Jagged 1 and 2 levels prevents cerebral arteriovenous malformations in matrix Gla protein deficiency

Yao, Yucheng; Yao, Jiayi; Radparvar, Melina; Blázquez‐Medela, Ana M.; Guihard, Pierre; Jumabay, Medet; Boström, Kristina I.

doi:10.1073/pnas.1310905110

Cited by 63 publications

(98 citation statements)

References 37 publications

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Section: Abstract: Mgp Angiogenesis Heart Development Brain Develmentioning

confidence: 99%

“…The increase of this BMP type I receptor enhances the expression of Notch ligands Jagged 1 and 2, which increases Notch activity and alters the expression of Ephrin-B2 and Ephrin receptor B4, arterial and venous endothelial markers, respectively. MGP is responsible for maintaining the balance between BMP and Notch signaling and promotes a normal brain vasculature (Yao et al, 2013). Furthermore, earlier in 2013 another study highlighted MGP importance during angiogenesis, namely in promoting angiogenic resolution and vascular stabilization (Sharma and Albig 2013).…”

Section: In Some Regions Of the Atrium (Yellow Hastag) And In The Sinmentioning

confidence: 99%

“…Biol. 60: 71-76 (2016) ( Yao et al, 2011), the maintenance of BMP and Notch signaling balance and the maintenance of normal endothelial cell function (Sharma and Albig, 2013;Yao et al, 2013).Nonetheless, MGP appears early in development, being expressed in a specific pattern in embryonic tissues, suggesting a developmentally regulated expression which could be associated to cell differentiation and proliferation (Cancela et al, 2014). In the avian embryo its expression was reported at E 14 in the aorta and at the base of the avian aortic valve predominantly in proteoglycan-rich spongiosa region and on the fibrosa surface of the valve (Alfieri et al, 2010).…”

mentioning

confidence: 99%

“…These functions include the regulation of calcium phosphate transport (Price et al, 2002), the activity of TGF-b1 (Bostrom et al, 2004), the inhibition of BMP2 (Wallin et al, 2000), BMP4, and BMP7 by direct binding (Yao et al, 2011), the maintenance of BMP and Notch signaling balance and the maintenance of normal endothelial cell function (Sharma and Albig, 2013;Yao et al, 2013).…”

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confidence: 99%

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Matrix Gla Protein expression pattern in the early avian embryo

Correia¹,

Conceição²,

Cancela³

et al. 2016

Int. J. Dev. Biol.

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MGP (Matrix Gla Protein) is an extracellular matrix vitamin K dependent protein previously identified as a physiological inhibitor of calcification and shown to be well conserved among vertebrates during evolution. MGP is involved in other mechanisms such as TGF-b and BMP activity, and a proposed modulator of cell-matrix interactions. MGP is expressed early in vertebrate development although its role has not been clarified. Previous work in the chicken embryo found MGP localization predominantly in the aorta and aortic valve base, but no data is available earlier in development. Here we examined MGP expression pattern using whole-mount in situ hybridization and histological sectioning during the initial stages of chick development. MGP was first detected at HH10 in the head and in the forming dorsal aorta. At the moment of the onset of blood circulation, MGP was expressed additionally in the venous plexus which will remodel into the vitelline arteries. By E2.25, it is clear that the vitelline arteries are MGP positive. MGP expression progresses centrifugally throughout the area vasculosa of the yolk sac. Between stages HH17 and HH19 MGP is seen in the dorsal aorta, heart, notochord, nephric duct, roof plate, vitelline arteries and in the yolk sac, beneath main arterial branches and in the vicinity of several vessels and venules. MGP expression persists in these areas at least until E4.5. These data suggest that MGP expression could be associated with cell migration and differentiation and to the onset of angiogenesis in the developing chick embryo. This data has biomedical relevance by pointing to the potential use of chick embryo explants to study molecules involved in artery calcification. KEY WORDS: MGP, angiogenesis, heart development, brain development, yolk sacMatrix Gla Protein (MGP) is a small secreted protein present in the extracellular matrix (ECM) that is known to be a physiological inhibitor of calcification. The correlation between the absence of functional MGP and aberrant calcification of both arteries and cartilage was clearly established following the development of the MGP knock-out mice (Luo et al., 1997). In humans, MGP mutations are the genetic basis of the Keutel syndrome (KS), a rare autosomal recessive disease characterized by abnormal cartilage calcification, brachytelephalangism, peripheral pulmonary artery stenosis, hearing loss, and facial abnormalities (Keutel et al., 1971;Hur et al., 2005).Multiple functions have been associated to MGP. These functions include the regulation of calcium phosphate transport (Price et al., 2002), the activity of TGF-b1 (Bostrom et al., 2004), the inhibition of BMP2 (Wallin et al., 2000), BMP4, and BMP7 by direct binding Int. J. Dev. Biol. 60: 71-76 (2016) ( Yao et al., 2011), the maintenance of BMP and Notch signaling balance and the maintenance of normal endothelial cell function (Sharma and Albig, 2013;Yao et al., 2013).Nonetheless, MGP appears early in development, being expressed in a specific pattern in embryonic tissues, suggesting a...

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Section: Abstract: Mgp Angiogenesis Heart Development Brain Develmentioning

confidence: 99%

Section: In Some Regions Of the Atrium (Yellow Hastag) And In The Sinmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Matrix Gla Protein expression pattern in the early avian embryo

Correia¹,

Conceição²,

Cancela³

et al. 2016

Int. J. Dev. Biol.

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“…ACVRL1 will inhibit BMP and induce Notch ligands, resulting in deregulation of endothelial differentiation and AVM development in MGP null animal models. 56 Activation of Notch4 (int-3) in the endothelium of animal models during brain development has been associated with AVM formation; it can be activated using a tetracycline-regulatable system. It has been demonstrated that int-3 activation alone is sufficient to induce and sustain the growth of abnormally large vasculature and shunting, which are the hallmarks of AVMs.…”

Section: Avm Formationmentioning

confidence: 99%

Molecular and cellular biology of cerebral arteriovenous malformations: a review of current concepts and future trends in treatment

Rangel-Castilla¹,

Russin²,

Martinez-del-Campo³

et al. 2014

FOC

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Object Arteriovenous malformations (AVMs) are classically described as congenital static lesions. However, in addition to rupturing, AVMs can undergo growth, remodeling, and regression. These phenomena are directly related to cellular, molecular, and physiological processes. Understanding these relationships is essential to direct future diagnostic and therapeutic strategies. The authors performed a search of the contemporary literature to review current information regarding the molecular and cellular biology of AVMs and how this biology will impact their potential future management. Methods A PubMed search was performed using the key words “genetic,” “molecular,” “brain,” “cerebral,” “arteriovenous,” “malformation,” “rupture,” “management,” “embolization,” and “radiosurgery.” Only English-language papers were considered. The reference lists of all papers selected for full-text assessment were reviewed. Results Current concepts in genetic polymorphisms, growth factors, angiopoietins, apoptosis, endothelial cells, pathophysiology, clinical syndromes, medical treatment (including tetracycline and microRNA-18a), radiation therapy, endovascular embolization, and surgical treatment as they apply to AVMs are discussed. Conclusions Understanding the complex cellular biology, physiology, hemodynamics, and flow-related phenomena of AVMs is critical for defining and predicting their behavior, developing novel drug treatments, and improving endovascular and surgical therapies.

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Mgp High‐Expressing MSCs Orchestrate the Osteoimmune Microenvironment of Collagen/Nanohydroxyapatite‐Mediated Bone Regeneration

Wan,

Bai,

Wang

et al. 2024

Advanced Science

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Activating autologous stem cells after the implantation of biomaterials is an important process to initiate bone regeneration. Although several studies have demonstrated the mechanism of biomaterial‐mediated bone regeneration, a comprehensive single‐cell level transcriptomic map revealing the influence of biomaterials on regulating the temporal and spatial expression patterns of mesenchymal stem cells (MSCs) is still lacking. Herein, the osteoimmune microenvironment is depicted around the classical collagen/nanohydroxyapatite‐based bone repair materials via combining analysis of single‐cell RNA sequencing and spatial transcriptomics. A group of functional MSCs with high expression of matrix Gla protein (Mgp) is identified, which may serve as a pioneer subpopulation involved in bone repair. Remarkably, these Mgp high‐expressing MSCs (MgphiMSCs) exhibit efficient osteogenic differentiation potential and orchestrate the osteoimmune microenvironment around implanted biomaterials, rewiring the polarization and osteoclastic differentiation of macrophages through the Mdk/Lrp1 ligand–receptor pair. The inhibition of Mdk/Lrp1 activates the pro‐inflammatory programs of macrophages and osteoclastogenesis. Meanwhile, multiple immune‐cell subsets also exhibit close crosstalk between MgphiMSCs via the secreted phosphoprotein 1 (SPP1) signaling pathway. These cellular profiles and interactions characterized in this study can broaden the understanding of the functional MSC subpopulations at the early stage of biomaterial‐mediated bone regeneration and provide the basis for materials‐designed strategies that target osteoimmune modulation.

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Reducing Jagged 1 and 2 levels prevents cerebral arteriovenous malformations in matrix Gla protein deficiency

Cited by 63 publications

References 37 publications

Matrix Gla Protein expression pattern in the early avian embryo

Matrix Gla Protein expression pattern in the early avian embryo

Molecular and cellular biology of cerebral arteriovenous malformations: a review of current concepts and future trends in treatment

Mgp High‐Expressing MSCs Orchestrate the Osteoimmune Microenvironment of Collagen/Nanohydroxyapatite‐Mediated Bone Regeneration

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