Abstract:
:Aberrant neovascularization contributes to diseases such as cancer, blindness and atherosclerosis, and is the consequence of inappropriate angiogenic signalling. Although many regulators of pathogenic angiogenesis have been identified, our understanding of this process is incomplete. Here we explore the transcriptome of retinal microvessels isolated from mouse models of retinal disease that exhibit vascular pathology, and uncover an upregulated gene, leucine-rich alpha-2-glycoprotein 1 (Lrg1), of previously unknown function. We show that in the presence of transforming growth factor-β1 (TGF-β1), LRG1 is mitogenic to endothelial cells and promotes angiogenesis. Mice lacking Lrg1 develop a mild retinal vascular phenotype but exhibit a significant reduction in pathological ocular angiogenesis. LRG1 binds directly to the TGF-β accessory receptor endoglin, which, in the presence of TGF-β1, results in promotion of the pro-angiogenic Smad1/5/8 signalling pathway. LRG1 antibody blockade inhibits this switch and attenuates angiogenesis. These studies reveal a new regulator of angiogenesis that mediates its effect by modulating TGF-β signalling.
journal_name
Naturejournal_title
Natureauthors
Wang X,Abraham S,McKenzie JAG,Jeffs N,Swire M,Tripathi VB,Luhmann UFO,Lange CAK,Zhai Z,Arthur HM,Bainbridge J,Moss SE,Greenwood Jdoi
10.1038/nature12345subject
Has Abstractpub_date
2013-07-18 00:00:00pages
306-11issue
7458eissn
0028-0836issn
1476-4687journal_volume
499pub_type
杂志文章相关文献
NATURE文献大全abstract:: ...
journal_title:Nature
pub_type: 新闻
doi:10.1038/d41586-019-00012-4
更新日期:2019-01-01 00:00:00
abstract::Cryptosporidium species cause acute gastroenteritis and diarrhoea worldwide. They are members of the Apicomplexa--protozoan pathogens that invade host cells by using a specialized apical complex and are usually transmitted by an invertebrate vector or intermediate host. In contrast to other Apicomplexans, Cryptosporid...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature02977
更新日期:2004-10-28 00:00:00
abstract::The Borrmann effect-a dramatic increase in transparency to X-ray beams-is observed when X-rays satisfying Bragg's law diffract through a perfect crystal. The minimization of absorption seen in the Borrmann effect has been explained by noting that the electric field of the X-ray beam approaches zero amplitude at the cr...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature07099
更新日期:2008-07-10 00:00:00
abstract::Approximately 2% of colorectal cancer is linked to pre-existing inflammation known as colitis-associated cancer, but most develops in patients without underlying inflammatory bowel disease. Colorectal cancer often follows a genetic pathway whereby loss of the adenomatous polyposis coli (APC) tumour suppressor and acti...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature11465
更新日期:2012-11-08 00:00:00
abstract::Transcriptional activator proteins (activators) function, at least in part, by increasing preinitiation complex assembly (for reviews see refs 1-4). Previous studies have shown that an acidic activator forms a contact with the general transcription factor TFIIB (refs 5-7) and recruits it into the preinitiation complex...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/371717a0
更新日期:1994-10-20 00:00:00
abstract::Water-driven fracture propagation beneath supraglacial lakes rapidly transports large volumes of surface meltwater to the base of the Greenland Ice Sheet. These drainage events drive transient ice-sheet acceleration and establish conduits for additional surface-to-bed meltwater transport for the remainder of the melt ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature14480
更新日期:2015-06-04 00:00:00
abstract::Macrophages are considered to contribute to chronic inflammatory diseases such as rheumatoid arthritis1. However, both the exact origin and the role of macrophages in inflammatory joint disease remain unclear. Here we use fate-mapping approaches in conjunction with three-dimensional light-sheet fluorescence microscopy...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-019-1471-1
更新日期:2019-08-01 00:00:00
abstract::Although infection by HIV-1 has been implicated as the primary cause of AIDS and related disorders, cofactorial mechanisms may be involved in the pathogenesis of the disease. For example, several viruses commonly detected in AIDS patients and capable of transactivating the long terminal repeat of HIV-1, such as herpes...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/337370a0
更新日期:1989-01-26 00:00:00
abstract::A model catalyst is described which has properties in common with carbonic anhydrase. The model demonstrates the availability of a mechanism, previously only hypothetical, for the action of the enzyme. It also shows, however, that this mechanism alone is not adequate to produce the high activity of the enzyme. ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/258677a0
更新日期:1975-12-25 00:00:00
abstract::Manic depression is a severe cyclic mental illness that can be unipolar or bipolar and has a lifetime risk of approximately 7 per 1,000 in most populations. Families with multiple cases of manic depression have been described that are compatible with both autosomal dominant and X-linked modes of genetic transmission. ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/325805a0
更新日期:1987-02-26 00:00:00
abstract::Oligonucleotide and complementary DNA microarrays are being used to subclassify histologically similar tumours, monitor disease progress, and individualize treatment regimens. However, extracting new biological insight from high-throughput genomic studies of human diseases is a challenge, limited by difficulties in re...
journal_title:Nature
pub_type: 临床试验,杂志文章
doi:10.1038/nature03985
更新日期:2005-10-13 00:00:00
abstract::Somatic mutations in the small GTPase K-Ras are the most common activating lesions found in human cancer, and are generally associated with poor response to standard therapies. Efforts to target this oncogene directly have faced difficulties owing to its picomolar affinity for GTP/GDP and the absence of known alloster...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature12796
更新日期:2013-11-28 00:00:00
abstract::A new gene, termed klotho, has been identified that is involved in the suppression of several ageing phenotypes. A defect in klotho gene expression in the mouse results in a syndrome that resembles human ageing, including a short lifespan, infertility, arteriosclerosis, skin atrophy, osteoporosis and emphysema. The ge...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/36285
更新日期:1997-11-06 00:00:00
abstract::Data collected at approximately 60 Global Positioning System (GPS) sites in southeast Asia show the crustal deformation caused by the 26 December 2004 Sumatra-Andaman earthquake at an unprecedented large scale. Small but significant co-seismic jumps are clearly detected more than 3,000 km from the earthquake epicentre...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature03937
更新日期:2005-07-14 00:00:00
abstract::Foreign protein antigens must be broken down within endosomes or lysosomes to generate suitable peptides that will form complexes with class II major histocompatibility complex molecules for presentation to T cells. However, it is not known which proteases are required for antigen processing. To investigate this, we e...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/25379
更新日期:1998-12-17 00:00:00
abstract::The formation of disulphide bonds is essential to the structure and function of proteins. These bonds rapidly form either cotranslationally or immediately post-translationally in the lumen of the endoplasmic reticulum. Native disulphide pairing for such proteins has been achieved in vitro; however, the rates of reasse...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/317267a0
更新日期:1985-09-19 00:00:00
abstract::Epidermal growth factor (EGF) and transforming growth factor type I (TGF) are polypeptides of 53 and 50 amino acid residues, respectively. Both bind to EGF receptor, a 1,200-residue transmembranous glycoprotein, leading to phosphorylation of the receptor, enhancement of its tyrosine-specific kinase activity and ultima...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/313491a0
更新日期:1985-02-07 00:00:00
abstract::Surface melt on the Greenland ice sheet has shown increasing trends in areal extent and duration since the beginning of the satellite era. Records for melt were broken in 2005, 2007, 2010 and 2012. Much of the increased surface melt is occurring in the percolation zone, a region of the accumulation area that is perenn...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature11566
更新日期:2012-11-08 00:00:00
abstract::During platelet activation there is a major reorganization in the platelet cytoskeleton that accompanies a rapid change in platelet shape. Many of the events associated with activation are attributed to a rise in calcium concentration within the platelet cytoplasm. One direct consequence of the elevated calcium is the...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/317449a0
更新日期:1985-10-03 00:00:00
abstract::alpha-Neurotoxins bind to cholinergic receptor, block transmission, and induce sprouting of retinal terminals in the toad tectum. New connections retain an orderliness that suggests a selective affinity between presynaptic terminals. The results suggest that postsynaptic cells exert a control, associated with receptor...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/269218a0
更新日期:1977-09-15 00:00:00
abstract::The lipopolysaccharide (LPS) of Gram negative bacteria is a well-known inducer of the innate immune response. Toll-like receptor (TLR) 4 and myeloid differentiation factor 2 (MD-2) form a heterodimer that recognizes a common 'pattern' in structurally diverse LPS molecules. To understand the ligand specificity and rece...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature07830
更新日期:2009-04-30 00:00:00
abstract::The isolation of a mutant adenovirus carrying an insertion of cellular DNA has led to the identification of a new family of human repetitive sequences, which are found tandemly arranged in the genome. The sequence of the viral insert resembles that of eukaryotic transposable elements. ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/302587a0
更新日期:1983-04-14 00:00:00
abstract::The mariner transposable element is a small member of the short inverted terminal repeat class thought to transpose through a DNA intermediate. Originally described in Drosophila mauritiana, it is now known in several species of the family Drosophilidae, and in a moth Hyalophora cecropia. Here I use primers designed t...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/362241a0
更新日期:1993-03-18 00:00:00
abstract::Gigantopithecus blacki was a giant hominid that inhabited densely forested environments of Southeast Asia during the Pleistocene epoch1. Its evolutionary relationships to other great ape species, and the divergence of these species during the Middle and Late Miocene epoch (16-5.3 million years ago), remain unclear2,3....
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-019-1728-8
更新日期:2019-12-01 00:00:00
abstract::An evolutionary view of ageing suggests that mortality may be due to an energy-saving strategy of reduced error regulation in somatic cells. This supports Orgel's 'error catastrophe' hypothesis and offers a new basis for the study of normal and abnormal ageing syndromes and of apparently immortal transformed cell line...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/270301a0
更新日期:1977-11-24 00:00:00
abstract::The biochemical response to food intake must be precisely regulated. Because ingested sugars and fats can feed into many anabolic and catabolic pathways1, how our bodies handle nutrients depends on strategically positioned metabolic sensors that link the intrinsic nutritional value of a meal with intermediary metaboli...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-018-0849-9
更新日期:2019-02-01 00:00:00
abstract:: ...
journal_title:Nature
pub_type: 新闻
doi:10.1038/d41586-018-07674-6
更新日期:2018-12-01 00:00:00
abstract::Quasicrystals are unique structures with long-range order but no periodicity. Their properties have intrigued scientists ever since their discovery and initial theoretical analysis. The lack of periodicity excludes the possibility of describing quasicrystal structures with well-established analytical tools, including ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature04722
更新日期:2006-04-27 00:00:00
abstract::Double-stranded RNAs (dsRNAs) induce post-transcriptional gene silencing in several species of animal and plant. In plants, dsRNAs targeted to CpG islands within a promoter can also induce RNA-directed DNA methylation; however, it remains unclear whether gene silencing mediated by DNA methylation can be induced by dsR...
journal_title:Nature
pub_type: 杂志文章,收录出版
doi:10.1038/nature02889
更新日期:2004-09-09 00:00:00
abstract::Dense plexuses of neurones containing immunoreactive vasoactive intestinal peptide (VIP) have been found in discrete areas of the central nervous system and in peripheral organs, including the gastrointestinal tract, pancreas and urogenital system. In many of these locations VIP is concentrated in nerve endings, where...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/281574a0
更新日期:1979-10-18 00:00:00