Abstract:
:Pathologic ocular neovascularization commonly causes blindness. It is critical to identify the factors altered in pathologically proliferating versus normally quiescent vessels to develop effective targeted therapeutics. MicroRNAs regulate both physiological and pathological angiogenesis through modulating expression of gene targets at the posttranscriptional level. However, it is not completely understood if specific microRNAs are altered in pathologic ocular blood vessels, influencing vascular eye diseases. Here we investigated the potential role of a specific microRNA, miR-150, in regulating ocular neovascularization. We found that miR-150 was highly expressed in normal quiescent retinal blood vessels and significantly suppressed in pathologic neovessels in a mouse model of oxygen-induced proliferative retinopathy. MiR-150 substantially decreased endothelial cell function including cell proliferation, migration, and tubular formation and specifically suppressed the expression of multiple angiogenic regulators, CXCR4, DLL4, and FZD4, in endothelial cells. Intravitreal injection of miR-150 mimic significantly decreased pathologic retinal neovascularization in vivo in both wild-type and miR-150 knockout mice. Loss of miR-150 significantly promoted angiogenesis in aortic rings and choroidal explants ex vivo and laser-induced choroidal neovascularization in vivo. In conclusion, miR-150 is specifically enriched in quiescent normal vessels and functions as an endothelium-specific endogenous inhibitor of pathologic ocular neovascularization.
journal_name
Proc Natl Acad Sci U S Aauthors
Liu CH,Sun Y,Li J,Gong Y,Tian KT,Evans LP,Morss PC,Fredrick TW,Saba NJ,Chen Jdoi
10.1073/pnas.1508426112subject
Has Abstractpub_date
2015-09-29 00:00:00pages
12163-8issue
39eissn
0027-8424issn
1091-6490pii
1508426112journal_volume
112pub_type
杂志文章abstract::Pseudoxanthoma elasticum (PXE) is an autosomal recessive disease characterized by progressive ectopic mineralization of the skin, eyes, and arteries, for which no effective treatment exists. PXE is caused by inactivating mutations in the gene encoding ATP-binding cassette sub-family C member 6 (ABCC6), an ATP-dependen...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1319582110
更新日期:2013-12-10 00:00:00
abstract::Preliminary x-ray diffraction data from single crystals of the MoFe proteins of nitrogenase from Clostridium pasteurianum and Azotobacter vinelandii have been obtained. Both protein crystals belong to the P2(1) space group. The MoFe protein crystals from C. pasteurianum and A. vinelandii diffract to angles correspondi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.79.2.378
更新日期:1982-01-01 00:00:00
abstract::Early events in both T-cell receptor (CD3)- and CD4-induced signal transduction pathways include tyrosine phosphorylation of protein substrates, the generation of phosphatidylinositol-phosphate breakdown products, and the mobilization of intracellular Ca2+. Oxidative stress in T cells mediated by sulfhydryl-reactive n...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.1.300
更新日期:1992-01-01 00:00:00
abstract::Murine embryonic stem (ES) cells were infected with a retrovirus promoter trap vector, and clones expressing lacZ fusion genes (LacZ+) were isolated by fluorescence-activated cell sorting (FACS). Of 12 fusion genes tested, 1 was repressed when ES cells were allowed to differentiate in vitro. Two of three lacZ fusion g...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.15.6721
更新日期:1992-08-01 00:00:00
abstract::Schizosaccharomyces pombe cells were transformed with an S. pombe expression vector containing a full-length cDNA of the Chlorella hexose transporter. The transformed cells accumulated 3-O-methylglucose up to 10-fold, whereas wild-type S. pombe and control transformants could only equilibrate this sugar analogue. In a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.20.7949
更新日期:1990-10-01 00:00:00
abstract::To scrutinize how a protein folds at atomic resolution, we performed 200 molecular dynamics simulations (each of 50 ns) of the miniprotein Trp-cage on the computational grid. Within the trajectories, 58 folding and 31 unfolding events were identified and subjected to extensive comparison and classification. Based on a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0407015102
更新日期:2004-12-21 00:00:00
abstract::The human eosinophil differentiation factor (EDF) gene was cloned from a genomic library in lambda phage EMBL3A by using a murine EDF cDNA clone as a probe. The DNA sequence of a 3.2-kilobase BamHI fragment spanning the gene was determined. The gene contains three introns. The predicted amino acid sequence of 134 amin...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.19.6629
更新日期:1987-10-01 00:00:00
abstract::Flowering time (i.e., heading date in crops) is an important ecological trait that determines growing seasons and regional adaptability of plants to specific natural environments. Rice (Oryza sativa L.) is a short-day plant that originated in the tropics. Increasing evidence suggests that the northward expansion of cu...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1213962110
更新日期:2013-02-19 00:00:00
abstract::Cell-surface labeling with fluorescamine indicates that the fluorescence of Balb 3T3 A31 cells in considerably decreased after both viral and chemical transformation. This phenomenon, coupled with the technique of flow microfluorometry, enabled nontransformed and transformed cells to be distinguished. A second fluroes...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.74.4.1626
更新日期:1977-04-01 00:00:00
abstract::Cell-based therapies, using multipotent mesenchymal stem cells (MSCs) for organ regeneration, are being pursued for cardiac disease, orthopedic injuries and biomaterial fabrication. The molecular pathways that regulate MSC-mediated regeneration or enhance their therapeutic efficacy are, however, poorly understood. We ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0803437105
更新日期:2008-11-25 00:00:00
abstract::Let t --> gamma(t), 0 = t = 1, be a smooth curve in IR(n). Define the maximal function [unk](f) by [unk](f)(x) = sup(0 journal_title:Proceedings of the National Academy of Sciences of the United States of America pub_type: 杂志文章 doi:10.1073/pnas.73.12.4295 更新日期:1976-12-01 00:00:00
abstract::Voltage gating of hyperpolarization-activated cation (HCN) channels is potentiated by direct binding of cAMP to a cytoplasmic cAMP-sensing domain (CSD). When unliganded, the CSD inhibits hyperpolarization-dependent opening of the HCN channel gate; cAMP binding relieves this autoinhibition so that opening becomes more ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1012750108
更新日期:2011-01-11 00:00:00
abstract::T follicular helper (Tfh) and regulatory (Tfr) cells are terminally differentiated cells found in germinal centers (GCs), specialized secondary lymphoid organ structures dedicated to antibody production. As such, follicular T (Tfol) cells are supposed to be specific for immunizing antigens, which has been reported for...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1808594115
更新日期:2018-09-18 00:00:00
abstract::We present a unique proxy for the reconstruction of variation in precipitation over the Amazon: oxygen isotope ratios in annual rings in tropical cedar (Cedrela odorata). A century-long record from northern Bolivia shows that tree rings preserve the signal of oxygen isotopes in precipitation during the wet season, wit...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1205977109
更新日期:2012-10-16 00:00:00
abstract::A series of HIV integrase (HIV-1 IN) inhibitors were synthesized to evaluate the role of the metal-binding group (MBG) in this class of metalloenzyme inhibitors. A total of 21 different raltegravir-chelator derivative (RCD) compounds were prepared that differed only in the nature of the MBG. These IN strand-transfer i...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1112389109
更新日期:2012-02-14 00:00:00
abstract::Aerobic respiration is a fundamental energy-generating process; however, there is cost associated with living in an oxygen-rich environment, because partially reduced oxygen species can damage cellular components. Organisms evolved enzymes that alleviate this damage and protect the intracellular milieu, most notably t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1505315112
更新日期:2015-08-25 00:00:00
abstract::Metabolism of [3-13C]alanine in the presence and absence of beta-hydroxybutyrate or ethanol has been followed at 25 degrees C by 13C NMR at 90.5 MHz in primary hepatocytes from untreated rats and rats treated with triiodothyronine and not allowed to eat for 24 hr. The phosphoenolpyruvate/pyruvate futile cycle was foll...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.78.1.60
更新日期:1981-01-01 00:00:00
abstract::Using a diverse collection of small molecules we recently found that compound sets from different sources (commercial; academic; natural) have different protein-binding behaviors, and these behaviors correlate with trends in stereochemical complexity for these compound sets. These results lend insight into structural ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1015024108
更新日期:2011-04-26 00:00:00
abstract::The sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) is a P-type ATPase that transports Ca2+ from the cytosol into the sarco(endo)plasmic reticulum (SR/ER) lumen, driven by ATP. This primary transport activity depends on tight coupling between movements of the transmembrane helices forming the two Ca2+-binding sites a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2014896117
更新日期:2020-12-08 00:00:00
abstract::The P23T mutant of human gammaD-crystallin (HGD) is associated with cataract. We have previously investigated the solution properties of this mutant, as well as those of the closely related P23V and P23S mutants, and shown that although mutations at site 23 of HGD do not produce a significant structural change in the ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0707412104
更新日期:2007-10-23 00:00:00
abstract::The present paper summarizes future needs in information and tools, technology, infrastructure, training, funding, and bioinformatics, to provide the genomic knowledge and tools for breeding and biotechnological goals in maize. The National Corn Genome Initiative (NCGA) has developed through actions taken by the Natio...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.5.2029
更新日期:1998-03-03 00:00:00
abstract::An 125I-labeled synthetic analog of bovine parathyroid hormone, [8-norleucine,18-norleucine,34-tyrosine]PTH-(1-34) amide ([Nle]PTH-(1-34)-NH2), purified by high-pressure liquid chromatography (HPLC), was employed to label the parathyroid hormone (PTH) receptor in cell lines derived from PTH target tissues: the ROS 17/...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.1.26
更新日期:1987-01-01 00:00:00
abstract::Thioredoxin (Trx) is an intracellular redox protein with extracellular cytokine-like and chemokine-like activities. We show here that, although plasma Trx levels are unrelated to survival of HIV-infected individuals with CD4 cell counts above 200/microl blood, survival is significantly impaired (P = 0.003) when plasma...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.041624998
更新日期:2001-02-27 00:00:00
abstract::Recently it has become apparent that N = 2 supersymmetric quantum field theory has something to do with cluster algebras. I review one aspect of the connection: supersymmetric quantum field theories have associated hyperkähler moduli spaces, and these moduli spaces carry a structure that looks like an extension of the...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1313073111
更新日期:2014-07-08 00:00:00
abstract::Anti-idiotype antibodies (Ab2) were purified from a cancer patient treated with NP-4, a murine monoclonal antibody to carcinoembryonic antigen (CEA). These Ab2 were specific for NP-4 and inhibited the binding between NP-4 and CEA. BALB/c mice immunized with these human Ab2 produced anti-Ab2 antibodies that were also r...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.8.3421
更新日期:1991-04-15 00:00:00
abstract::The activities of cytosolic 3-hydroxy-3-methylglutaryl coenzyme A synthase [3-hydroxy-3-methylglutaryl-CoA acetoacetyl-CoA-lyase (CoA-acylating), EC 4.1.3.5] and microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase[mevalonate:NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34], two sequential enzymes in the chole...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.74.4.1421
更新日期:1977-04-01 00:00:00
abstract::Lethal factor, the principal virulence factor of Bacillus anthracis, inhibits mitogen-activated protein kinase (MAPK) signaling by proteolytically cleaving MAPK kinases. Edema factor, another component of anthrax toxin, is an adenylate cyclase, which increases intracellular cAMP. Inhibition of MAPK signaling with eith...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.052707699
更新日期:2002-03-05 00:00:00
abstract::In the developing cerebellum, switching of the subunit composition of NMDA receptors occurs in granule cells from NR2B-containing receptors to NR2C-containing ones. We investigated the mechanisms underlying switching of NR2B and NR2C subunit composition in primary cultures of mouse granule cells at the physiological K...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0805574105
更新日期:2008-08-19 00:00:00
abstract::Total chemical synthesis was used to prepare the mirror image (D-protein) form of the angiogenic protein vascular endothelial growth factor (VEGF-A). Phage display against D-VEGF-A was used to screen designed libraries based on a unique small protein scaffold in order to identify a high affinity ligand. Chemically syn...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1210483109
更新日期:2012-09-11 00:00:00
abstract::Sprouty proteins act as intracellular inhibitors of receptor tyrosine kinase signaling. Here we show that the mammalian Sprouty2 protein contains an iron-sulfur complex that can exist in an oxidized, reduced, or nitrosylated state. Purified Sprouty2 assembles into large monodisperse spheres containing approximately 24...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0506714102
更新日期:2005-09-27 00:00:00