Production of the transforming growth factor-β binding protein endoglin is regulated during chick heart development

Vincent, Eric B.; Runyan, Raymond B.; Weeks, Daniel L.

doi:10.1002/(sici)1097-0177(199811)213:3<237::aid-aja1>3.0.co;2-m

Cited by 22 publications

(20 citation statements)

References 34 publications

(13 reference statements)

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“…Furthermore, mutations in the endoglin gene lead to haploinsufficiency and are responsible for the hereditary hemorrhagic telangiectasia type 1 (HHT1), an autosomal dominant disorder characterized by multisystemic vascular dysplasia, and recurrent hemorrhage (Guttmacher et al, 1995;Shovlin and Letarte, 1999;Marchuk and Lux, 2001). In addition, endoglin expression is regulated during heart development in human and chicken (Qu et al, 1998;Vincent et al, 1998); and endoglin-null mice obtained by targeted disruption of the endoglin gene die at 10-10.5 days post coitum due to vascular and cardiac abnormalities (Bourdeau et al, 1999;Li et al, 1999;Arthur et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Expression of the TGF-β coreceptor endoglin in epidermal keratinocytes and its dual role in multistage mouse skin carcinogenesis

et al. 2003

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Endoglin is an integral membrane glycoprotein primarily expressed in the vascular endothelium, but also found on macrophages and stromal cells. It binds several members of the transforming growth factor (TGF)-b family of growth factors and modulates TGF-b 1 -dependent cellular responses. However, it lacks cytoplasmic signaling motifs and is considered as an auxiliary receptor for TGF-b. We show here that endoglin is expressed in mouse and human epidermis and in skin appendages, such as hair follicles and sweat glands, as determined by immunohistochemistry. In normal interfollicular epidermis, endoglin was restricted to basal keratinocytes and absent in differentiating cells of suprabasal layers. Follicular expression of endoglin was high in hair bulb keratinocytes, but decreased in parts distal from the bulb. To address the role of endoglin in skin carcinogenesis in vivo, Endoglin heterozygous mice were subjected to long-term chemical carcinogenesis treatment. Reduction in endoglin had a dual effect during multistage carcinogenesis, by inhibiting the early appearance of benign papillomas, but increasing malignant progression to highly undifferentiated carcinomas. Our results are strikingly similar to those previously reported for transgenic mice overexpressing TGF-b 1 in the epidermis. These data suggest that endoglin might attenuate TGF-b 1 signaling in normal epidermis and interfere with progression of skin carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Expression of the TGF-β coreceptor endoglin in epidermal keratinocytes and its dual role in multistage mouse skin carcinogenesis

et al. 2003

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“…All 3 isoforms of TGF-β, and TβRII, have been implicated in cushion-tissue formation in vitro (33)(34)(35)(36). Endoglin is detected on chicken mesenchymal cells undergoing transformation and migrating into the cushion tissue, closely following the expression of the TGF-β3 isoform (37). It was proposed that betaglycan might be the component of the TGF-β receptor system responsible for endocardial cell trans- formation (38).…”

Section: Figurementioning

confidence: 99%

A murine model of hereditary hemorrhagic telangiectasia

Bourdeau¹,

Dumont²,

Letarte³

1999

J. Clin. Invest.

434

419

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Endoglin (CD105), an accessory protein of the TGF-β receptor superfamily, is highly expressed on endothelial cells. Hereditary hemorrhagic telangiectasia type 1 (HHT1) is associated with mutations in the Endoglin gene, leading to haploinsufficiency. To generate a disease model and ascertain the role of endoglin in development, we generated mice lacking 1 or both copies of the gene. Endoglin null embryos die at gestational day 10.0-10.5 due to defects in vessel and heart development. Vessel formation appears normal until hemorrhage occurs in yolk sacs and embryos. The primitive vascular plexus of the yolk sac fails to mature into defined vessels, and vascular channels dilate and rupture. Internal bleeding is seen in the peritoneal cavity, implying fragile vessels. Heart development is arrested at day 9.0, and the atrioventricular canal endocardium fails to undergo mesenchymal transformation and cushion-tissue formation. These data suggest that endoglin is critical for both angiogenesis and heart valve formation. Some heterozygotes, either with an inbred 129/Ola or mixed C57BL/6-129/Ola background, show signs of HHT, such as telangiectases or recurrent nosebleeds. In this murine model of HHT, it appears that epigenetic factors and modifier genes, some of which are present in 129/Ola, contribute to disease heterogeneity.

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“…It is highly expressed on endothelial cells and several lines of evidence support an important role for endoglin in cardiovascular development and vascular remodeling. Thus, endoglin expression is regulated during heart development in humans and chicken (15,16), and genetic inactivation of endoglin in the mouse shows that embryos homozygous for mutant endoglin die at 10 -10.5 days postcoitum due to vascular and cardiac anomalies (17)(18)(19). Furthermore, genes encoding endoglin and ALK-1 (a type I TGF-␤ receptor) are targets for the autosomal dominant disorder known as hereditary hemorrhagic telangiectasia (20 -22).…”

Section: Members Of the Transforming Growth Factor-␤ (Tgf-␤)mentioning

confidence: 99%

Extracellular and Cytoplasmic Domains of Endoglin Interact with the Transforming Growth Factor-β Receptors I and II

Guerrero-Esteo¹,

Sánchez-Elsner²,

Letamendı́a³

et al. 2002

Journal of Biological Chemistry

206

213

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Endoglin is an auxiliary component of the transforming growth factor-␤ (TGF-␤) receptor system, able to associate with the signaling receptor types I (T␤RI) and II (T␤RII) in the presence of ligand and to modulate the cellular responses to TGF-␤1. Endoglin cannot bind ligand on its own but requires the presence of the signaling receptors, supporting a critical role for the interaction between endoglin and T␤RI or T␤RII. This study shows that full-length endoglin interacts with both T␤RI and T␤RII, independently of their kinase activation state or the presence of exogenous TGF-␤1. Truncated constructs encoding either the extracellular or the cytoplasmic domains of endoglin demonstrated that the association with the signaling receptors occurs through both extracellular and cytoplasmic domains. However, a more specific mapping revealed that the endoglin/T␤RI interaction was different from that of endoglin/T␤RII. T␤RII interacts with the amino acid region 437-558 of the extracellular domain of endoglin, whereas T␤RI interacts not only with the region 437-558 but also with the protein region located between amino acid 437 and the N terminus. Both T␤RI and T␤RII interact with the cytoplasmic domain of endoglin, but T␤RI only interacts when the kinase domain is inactive, whereas T␤RII remains associated in its active and inactive forms. Upon association, T␤RI and T␤RII phosphorylate the endoglin cytoplasmic domain, and then T␤RI, but not T␤RII, kinase dissociates from the complex. Conversely, endoglin expression results in an altered phosphorylation state of T␤RII, T␤RI, and downstream Smad proteins as well as a modulation of TGF-␤ signaling, as measured by the reporter gene expression. These results suggest that by interacting through its extracellular and cytoplasmic domains with the signaling receptors, endoglin might affect TGF-␤ responses.

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Production of the transforming growth factor-β binding protein endoglin is regulated during chick heart development

Cited by 22 publications

References 34 publications

Expression of the TGF-β coreceptor endoglin in epidermal keratinocytes and its dual role in multistage mouse skin carcinogenesis

Expression of the TGF-β coreceptor endoglin in epidermal keratinocytes and its dual role in multistage mouse skin carcinogenesis

A murine model of hereditary hemorrhagic telangiectasia

Extracellular and Cytoplasmic Domains of Endoglin Interact with the Transforming Growth Factor-β Receptors I and II

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