Disease relevance of ENG

• Hereditary hemorrhagic telangiectasia: ENG and ALK-1 mutations in Dutch patients [1].
• Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disease characterized by arteriovenous malformations and resulting from mutations in two major genes: ENG and ACVRL1 [2].
• Hereditary haemorrhagic telangiectasia, or Osler-Rendu-Weber (ORW) syndrome, is an autosomal dominant vascular dysplasia [3].
• We found that epistaxis had an earlier onset in patients with HHT1 than those with HHT2, but the severity by middle ages was similar [4].
• These results show that CD105 is expressed specifically in the tumor angiogenesis of brain, lung, breast, stomach, and colon cancers [5].
• Neurological manifestations secondary to CAVMs/PAVMs were found only in HHT1 patients, whereas severe liver involvement was detected only in HHT2 [6].
• Preoperative plasma endoglin levels are associated with established features of advanced prostate cancer [7].

Psychiatry related information on ENG

• Single fibre ENG needs more patient cooperation than do these tests [8].
• Vestibular ENG findings in a patient with agoraphobia [9].
• The ENG gave 3 false-negatives whereas the results of speech discrimination tests were misleading in no fewer than 1/3 of the cases [10].

High impact information on ENG

• We report three mutations in the coding sequence of the ALK1 gene in those families which show linkage of the ORW phenotype to chromosome 12 [3].
• Linkage studies established an ORW locus at chromosome 9q3; endoglin was subsequently identified as the ORW1 gene [3].
• Endoglin (CD105), an accessory protein of the TGF-beta receptor superfamily, is highly expressed on endothelial cells [11].
• Endoglin (CD105), a component of the TGF-beta 1 receptor complex, is the target gene for the dominantly inherited vascular disorder hereditary hemorrhagic telangiectasia type 1 (HHT1) [12].
• Microarray analysis revealed that CEACAM engagement by several human pathogens triggers expression of CD105 [13].

Chemical compound and disease context of ENG

• A degree of reticulin fibrosis >2 correlated with increased CD105 MVD (P=0.05) [14].
• Clinical and ENG data showed the neuromuscular location of the ophthalmoplegia, but repeated Tensilon and Prostigmine tests were negative [15].
• BACKGROUND AND PURPOSE: Endoglin (CD105) is a membrane glycoprotein that is mutated in hereditary hemorrhagic telangiectasia (Osler-Rendu-Weber disease) and shows increased expression in proliferating endothelial cells during angiogenesis [16].

Biological context of ENG

• Novel mutations in ENG and ACVRL1 identified in a series of 200 individuals undergoing clinical genetic testing for hereditary hemorrhagic telangiectasia (HHT): correlation of genotype with phenotype [17].
• Truncating mutations in ENG were associated with more affected organs and more severe hemorrhaging than were missense mutations [4].
• Mutations in ACVRL1 cluster largely in exons 7 and 8, but ENG mutations were widely distributed within that gene [4].
• Genetic heterogeneity of HHT is confirmed; 2 disease loci, ACVRL1 and ENG genes, have been identified and characterized [18].
• Interestingly, endoglin up-regulation was deficient in activated monocytes of both HHT1 and HHT2 patients compared with controls [19].

Anatomical context of ENG

• The TGFB signalling associated receptors ENG and ALK1 were co-expressed in 4 of the cell lines [20].
• In the current study, umbilical cord and placenta samples from newborns with ENG mutations were analyzed to estimate the level of corresponding protein and look for potential vascular dysplasia [21].
• Thus, blood vessels from HHT1 individuals are maintained intact in the umbilical vein and placenta during pregnancy and delivery, despite a significant reduction in endoglin expression [21].
• We observed significantly lower values in the HHT1 group, compared to the non-HHT group for the umbilical vein (n=9; median 0.6 vs 0.9; ranges 0.2-1.0 and 0.5-1.5) and for placental stem villus vessels (n=9 and 10; median 0.42 vs 0.93; ranges 0.24-0.58 and 0.56-1.18) [21].
• CD105 expression was intense and restricted to capillary endothelial cells in cancer lesions (>73%) [5].

Associations of ENG with chemical compounds

• Endoglin (CD105) is a transmembrane glycoprotein that binds transforming growth factor (TGF)-beta1 and -beta3, and coprecipitates with the Ser/Thr kinase signaling receptor complex by affinity labeling of endothelial and leukemic cells [22].
• CD4(+) T cells constitutively expressed CD105 in memory T cells and partially also in naive T cells; however, surface expression is regulated and is increased following TCR engagement, which induced serine/threonine phosphorylation of CD105 [23].
• When analysing patient 700/01 and his affected daughter, we encountered a mutant ENG allele with two mutations--a deletion in exon 7 and a substitution in exon 12--which converts isoleucine 575 into threonine, in a non-conserved region [24].
• Use of Implanon (etonogestrel subdermal implant, referred to herein as ENG implant) for up to 2 years had no clinically significant effects on laboratory parameters, physical and pelvic examinations, vital signs or body mass index [25].
• Apoprotein A-I (Apo A-I) increased by 9% with ENA and by 11% with EED (p less than 0.05), but did not change significantly with ENG [26].

Regulatory relationships of ENG

• TNF alpha down-regulates CD105 expression in vascular endothelial cells: a comparative study with TGF beta 1 [27].
• A small subset of human CD34+ hematopoietic stem/progenitor cells that has phenotypic and functional features suggestive of very primitive hematopoietic cells expresses the CD105 antigen [28].
• CD105 is almost universally expressed in microvessels within the atheroma and is therefore a better vascular marker than CD31 and TGFbeta(1) for assessing neovascularisation in atherosclerotic plaques [29].
• Our results showed that there is a subpopulation of granule-rich, CD105 positive and von Willebrand antigen negative endothelial cells that have an enhanced basal expression of ICAM-1, and Fas antigen, but, interestingly, no apoptotic bodies were detected [30].
• By measuring Smad-specific phosphorylation and Smad-responsive promoter activity, endoglin was shown to constitutively activate Smad1, with little-to-no effect upon Smad3 [31].
• Addition of TGF-beta 3 to villous explants under low oxygen conditions increased the expression of endoglin compared to nontreated explants whereas addition of TGF-beta 3-neutralizing antibodies inhibited the low oxygen stimulatory effect on endoglin expression [32].

Other interactions of ENG

• Those adhesions expressing vascular endothelial growth factor A and its receptor showed significantly higher numbers of immature vessels as defined by expression of CD105 [33].
• Functional blood vessels expressed recognized vascular markers (vWF, CD34, alpha-SMA, and CD105) and formed a branching network similar to that of the peritoneum [33].
• KDR, ENG and FLT4 were all compatible with linkage, with haplotypes being shared between three affected individuals and the one obligate carrier available for testing [34].
• Unlike traditional mesenchymal stem cells derived from adult bone marrow stromal cells, small populations of UCMS cells express endoglin (SH2, CD105) and CD49e at passage 8 [35].
• By using human dermal microvascular endothelial cells the present study has shown that long-term treatment with TNF alpha (0.1-5 ng/ml) elicited a concentration- and time-dependent significant suppression (over 50% reduction) in CD105 protein levels [27].

Analytical, diagnostic and therapeutic context of ENG

• We report here on the genetic and molecular heterogeneity found in the HHT population in the Netherlands. Probands of 104 apparently unrelated families were studied and we performed sequence analysis on both the ENG gene and ALK-1 gene [1].
• However, in the absence of ligand, ALK-1 and endoglin interactions were observed by immunoprecipitation/western blot in HUVEC from normal as well as HHT1 and HHT2 patients [36].
• ENG sequences of affected members of the four linked families and probands from the 24 small families were screened for mutations, by Southern blot analyses and by cycle sequencing of PCR-amplified DNA [37].
• TGF-beta1 and CD105 in 55 gastric carcinoma tissues on the same slide were detected by using double-stain Immunohistochemistry (DS-ABC) [38].
• Endothelial cells (ECs) were detected by immunofluorescent staining for CD31 or CD105, and MYCN amplification was detected using fluorescence in situ hybridization (FISH) [39].

References