Endoglin regulates renal ischaemia–reperfusion injury

Docherty, Neil G.; López‐Novoa, José M.; Arévalo, Miguel; Düwel, Annette; Rodríguez-Peña, Ana B.; Pérez‐Barriocanal, Fernando; Bernabeu, Carmelo; Eleno, Nélida

doi:10.1093/ndt/gfl179

Cited by 44 publications

(44 citation statements)

References 28 publications

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“…MNC adherence to the vessel wall is regulated by a family of membrane molecules called cell adhesion molecules (CAMs), including ICAM-1, VCAM-1, PECAM-1, and P-selectin. After renal ischemia-reperfusion, both CAM expression and MNC infiltration were reduced in Eng ϩ/Ϫ compared with wild-type mice (47). Thus a defective CAM expression in endoglin-deficient cells (either in endothelial or circulating cells) could also explain the low angiogenesis rate associated with endoglin deficiency.…”

Section: Endoglin and Regulation Of Vascular Repairmentioning

confidence: 96%

“…Endoglin is expressed at low levels in resting ECs, but it is highly expressed in vascular ECs at sites of active angiogenesis, during embryogenesis (80,131), and in inflamed tissues and healing wounds (163), psoriatic skin (145), inflamed synovial arthritis (155), upon vascular injury (21), and in tumor vessels (13,25,55,119). Endoglin is also overexpressed after ischemia and reperfusion in the kidney (47), hindlimbs (79), and heart (168). Endoglin is expressed not only in ECs but also in several other cell types involved in the cardiovascular system.…”

Section: Regulation Of Endoglin Expressionmentioning

confidence: 99%

“…In fact, endoglin expression is upregulated after ischemia in the heart (168), kidney (47), and hindlimbs (79), as well as upon arterial injury (21,110). Also, in murine cerebral microvascular ECs, hypoxia induces the expression of endoglin at both the mRNA and protein levels, and this induction is regulated by p38 and probably JNK pathways (179).…”

Section: Regulation Of Endoglin Expressionmentioning

confidence: 99%

“…To explain this finding, one can postulate the need for an external trigger, or second hit, such as inflammation, infection, vascular injury, ischemia, or trauma that synergizes with endoglin haploinsufficiency to generate the lesion. Of note, these potential hits can upregulate endoglin expression (21,34,47,90,110,146,163,167,168), suggesting that endoglin function is required under those stressing conditions. Experimental support for the second hit hypothesis has been recently reported using a mouse with a conditional mutation in Eng, demonstrating that AVMs develop when an angiogenic stimulus is combined with endoglin depletion (112).…”

Section: Role Of Endoglin In Vascular Pathologymentioning

confidence: 99%

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The physiological role of endoglin in the cardiovascular system

López‐Novoa

Bernabeu

2010

American Journal of Physiology-Heart and Circulatory Physiology

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185

197

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Endoglin (CD105) is an integral membrane glycoprotein that serves as a coreceptor for members of the transforming growth factor-β superfamily of proteins. A major role for endoglin in regulating transforming growth factor-β-dependent vascular remodeling and angiogenesis has been postulated based on the following: 1) endoglin is the gene mutated in hereditary hemorrhagic telangiectasia type 1, a disease characterized by vascular malformations; 2) endoglin knockout mice die at midgestation because of defective angiogenesis; 3) endoglin is overexpressed in neoangiogenic vessels, during inflammation, and in solid tumors; and 4) endoglin regulates the expression and activity of endothelial nitric oxide synthase, which is involved in angiogenesis and vascular tone. Besides the predominant form of the endoglin receptor (long endoglin isoform), two additional forms of endoglin have been recently reported to play a role in the vascular pathology and homeostasis: the alternatively spliced short endoglin isoform and a soluble endoglin form that is proteolytically cleaved from membrane-bound endoglin. The purpose of this review is to underline the role that the different forms of endoglin play in regulating angiogenesis, vascular remodeling, and vascular tone, as well as to analyze the molecular and cellular mechanisms supporting these effects.

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Section: Endoglin and Regulation Of Vascular Repairmentioning

confidence: 96%

Section: Regulation Of Endoglin Expressionmentioning

confidence: 99%

Section: Regulation Of Endoglin Expressionmentioning

confidence: 99%

Section: Role Of Endoglin In Vascular Pathologymentioning

confidence: 99%

See 2 more Smart Citations

The physiological role of endoglin in the cardiovascular system

López‐Novoa

Bernabeu

2010

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

185

197

View full text Add to dashboard Cite

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“…Lung samples of powdered tissue were processed and myeloperoxidase (MPO) activity was measured following the Bradley method modified by Mullane. 22 Tissue sections (3 m) from lung were stained with hematoxylin and eosin or with the monoclonal anti-CD68 (Dako) antibody, followed by the secondary antibody Alexa488 antimouse IgG (Life Technologies). …”

mentioning

confidence: 99%

Endothelial endoglin is involved in inflammation: role in leukocyte adhesion and transmigration

Rossi

Sanz-Rodrı́guez

Eleno

et al. 2013

Blood

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135

148

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Key Points• Endothelial endoglin has a regulatory role in leukocyte trafficking through vascular endothelia.• Leukocytes and endothelial cells interact via integrin receptors and endoglin, being this cell adhesion process stimulated by inflammatory stimuli.Human endoglin is an RGD-containing transmembrane glycoprotein identified in vascular endothelial cells. Although endoglin is essential for angiogenesis and its expression is up-regulated in inflammation and at sites of leukocyte extravasation, its role in leukocyte trafficking is unknown. This function was tested in endoglin heterozygous mice (Eng ؉/؊ ) and their wild-type siblings Eng ؉/؉ treated with carrageenan or LPS as inflammatory agents. Both stimuli showed that inflammation-induced leukocyte transendothelial migration to peritoneum or lungs was significantly lower in Eng ؉/؊ than in Eng ؉/؉ mice. Leukocyte transmigration through cell monolayers of endoglin transfectants was clearly enhanced in the presence of endoglin. Coating transwells with the RGD-containing extracellular domain of endoglin, enhanced leukocyte transmigration, and this increased motility was inhibited by soluble endoglin. Leukocytes stimulated with CXCL12, a chemokine involved in inflammation, strongly adhered to endoglincoated plates and to endoglin-expressing endothelial cells. This endoglin-dependent adhesion was abolished by soluble endoglin, RGD peptides, the anti-integrin ␣5␤1 inhibitory antibody LIA1/2 and the chemokine receptor inhibitor AMD3100. These results demonstrate for the first time that endothelial endoglin interacts with leukocyte integrin ␣5␤1 via its RGD motif, and this adhesion process is stimulated by the inflammatory chemokine CXCL12, suggesting a regulatory role for endoglin in transendothelial leukocyte trafficking. (Blood. 2013;121(2):403-415) IntroductionThe vascular endothelium controls the transit of white blood cells into and out of the bloodstream. The migration of leukocytes involves the adhesive interaction of cell surface receptors with ligands expressed on endothelial cells in a process regulated by inflammatory stimuli. Stromal-derived factor 1 (SDF1␣), renamed CXCL12, is a potent chemoattractant for a variety of cells including lymphocytes, monocytes, dendritic cells, and hematopoietic stem cells. 1 CXCL12 and its receptor CXCR4 play relevant roles in immune and inflammatory responses, including leukocyte migration and recruitment, as well as integrin-dependent adhesion and transendothelial migration. 1 CXCL12 is a critical activator of endothelial progenitors by inducing a proangiogenic phenotype and increasing migration and rolling mediated by ␣4 and ␣M integrin subunits. 2 The process of leukocyte migration through the endothelial cell monolayer involves an interaction between leukocytes' integrins and endothelial-cell receptors, both acting as adhesion molecules. Integrins most relevant to leukocytes belong to the ␤ 1 -integrin and the ␤ 2 -integrin subfamilies. Classic chemoattractants and chemokines are the most powerful physiologic activat...

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