Endothelial microRNA-150 is an intrinsic suppressor of pathologic ocular neovascularization.

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.

authors

Liu CH,Sun Y,Li J,Gong Y,Tian KT,Evans LP,Morss PC,Fredrick TW,Saba NJ,Chen J

doi

10.1073/pnas.1508426112

subject

Has Abstract

pub_date

2015-09-29 00:00:00

pages

12163-8

issue

39

eissn

0027-8424

issn

1091-6490

pii

1508426112

journal_volume

112

pub_type

杂志文章
  • ABCC6 prevents ectopic mineralization seen in pseudoxanthoma elasticum by inducing cellular nucleotide release.

    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

    authors: Jansen RS,Küçükosmanoglu A,de Haas M,Sapthu S,Otero JA,Hegman IE,Bergen AA,Gorgels TG,Borst P,van de Wetering K

    更新日期:2013-12-10 00:00:00

  • Crystallographic properties of the MoFe proteins of nitrogenase from Clostridium pasteurianum and Azotobacter vinelandii.

    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

    authors: Weininger MS,Mortenson LE

    更新日期:1982-01-01 00:00:00

  • Sulfhydryl oxidation down-regulates T-cell signaling and inhibits tyrosine phosphorylation of phospholipase C gamma 1.

    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

    authors: Kanner SB,Kavanagh TJ,Grossmann A,Hu SL,Bolen JB,Rabinovitch PS,Ledbetter JA

    更新日期:1992-01-01 00:00:00

  • Fluorescence-activated sorting of totipotent embryonic stem cells expressing developmentally regulated lacZ fusion genes.

    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

    authors: Reddy S,Rayburn H,von Melchner H,Ruley HE

    更新日期:1992-08-01 00:00:00

  • Functional expression of the Chlorella hexose transporter in Schizosaccharomyces pombe.

    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

    authors: Sauer N,Caspari T,Klebl F,Tanner W

    更新日期:1990-10-01 00:00:00

  • Phylogeny of protein-folding trajectories reveals a unique pathway to native structure.

    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

    authors: Ota M,Ikeguchi M,Kidera A

    更新日期:2004-12-21 00:00:00

  • Molecular cloning, nucleotide sequence, and expression of the gene encoding human eosinophil differentiation factor (interleukin 5).

    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

    authors: Campbell HD,Tucker WQ,Hort Y,Martinson ME,Mayo G,Clutterbuck EJ,Sanderson CJ,Young IG

    更新日期:1987-10-01 00:00:00

  • Association of functional nucleotide polymorphisms at DTH2 with the northward expansion of rice cultivation in Asia.

    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

    authors: Wu W,Zheng XM,Lu G,Zhong Z,Gao H,Chen L,Wu C,Wang HJ,Wang Q,Zhou K,Wang JL,Wu F,Zhang X,Guo X,Cheng Z,Lei C,Lin Q,Jiang L,Wang H,Ge S,Wan J

    更新日期:2013-02-19 00:00:00

  • Quantitative determination of transformed cells in a mixed population by stimultaneous fluorescence analysis of cell surface and DNA an individual cells.

    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

    authors: Hawkes SP,Bartholomew JC

    更新日期:1977-04-01 00:00:00

  • The Wnt modulator sFRP2 enhances mesenchymal stem cell engraftment, granulation tissue formation and myocardial repair.

    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

    authors: Alfaro MP,Pagni M,Vincent A,Atkinson J,Hill MF,Cates J,Davidson JM,Rottman J,Lee E,Young PP

    更新日期:2008-11-25 00:00:00

  • Maximal functions associated to smooth curves.

    abstract::Let t --> gamma(t), 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

    authors: Stein EM,Wainger S

    更新日期:1976-12-01 00:00:00

  • Cytoplasmic cAMP-sensing domain of hyperpolarization-activated cation (HCN) channels uses two structurally distinct mechanisms to regulate voltage gating.

    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

    authors: Wicks NL,Wong T,Sun J,Madden Z,Young EC

    更新日期:2011-01-11 00:00:00

  • High-resolution repertoire analysis reveals a major bystander activation of Tfh and Tfr cells.

    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

    authors: Ritvo PG,Saadawi A,Barennes P,Quiniou V,Chaara W,El Soufi K,Bonnet B,Six A,Shugay M,Mariotti-Ferrandiz E,Klatzmann D

    更新日期:2018-09-18 00:00:00

  • Oxygen isotopes in tree rings are a good proxy for Amazon precipitation and El Nino-Southern Oscillation variability.

    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

    authors: Brienen RJ,Helle G,Pons TL,Guyot JL,Gloor M

    更新日期:2012-10-16 00:00:00

  • Probing chelation motifs in HIV integrase inhibitors.

    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

    authors: Agrawal A,DeSoto J,Fullagar JL,Maddali K,Rostami S,Richman DD,Pommier Y,Cohen SM

    更新日期:2012-02-14 00:00:00

  • Adaptive aneuploidy protects against thiol peroxidase deficiency by increasing respiration via key mitochondrial proteins.

    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

    authors: Kaya A,Gerashchenko MV,Seim I,Labarre J,Toledano MB,Gladyshev VN

    更新日期:2015-08-25 00:00:00

  • 13C NMR study of gluconeogenesis from labeled alanine in hepatocytes from euthyroid and hyperthyroid rats.

    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

    authors: Cohen SM,Glynn P,Shulman RG

    更新日期:1981-01-01 00:00:00

  • Quantifying structure and performance diversity for sets of small molecules comprising small-molecule screening collections.

    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

    authors: Clemons PA,Wilson JA,Dančík V,Muller S,Carrinski HA,Wagner BK,Koehler AN,Schreiber SL

    更新日期:2011-04-26 00:00:00

  • The SERCA residue Glu340 mediates interdomain communication that guides Ca2+ transport.

    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

    authors: Geurts MMG,Clausen JD,Arnou B,Montigny C,Lenoir G,Corey RA,Jaxel C,Møller JV,Nissen P,Andersen JP,le Maire M,Bublitz M

    更新日期:2020-12-08 00:00:00

  • Altered phase diagram due to a single point mutation in human gammaD-crystallin.

    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

    authors: McManus JJ,Lomakin A,Ogun O,Pande A,Basan M,Pande J,Benedek GB

    更新日期:2007-10-23 00:00:00

  • Potentials of the National Corn Genome Initiative.

    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

    authors: Coe EH

    更新日期:1998-03-03 00:00:00

  • Immunoprecipitation of the parathyroid hormone receptor.

    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

    authors: Wright BS,Tyler GA,O'Brien R,Caporale LH,Rosenblatt M

    更新日期:1987-01-01 00:00:00

  • Chronic elevation of plasma thioredoxin: inhibition of chemotaxis and curtailment of life expectancy in AIDS.

    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

    authors: Nakamura H,De Rosa SC,Yodoi J,Holmgren A,Ghezzi P,Herzenberg LA,Herzenberg LA

    更新日期:2001-02-27 00:00:00

  • Cluster-like coordinates in supersymmetric quantum field theory.

    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

    authors: Neitzke A

    更新日期:2014-07-08 00:00:00

  • Human response against NP-4, a mouse antibody to carcinoembryonic antigen: human anti-idiotype antibodies mimic an epitope on the tumor antigen.

    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

    authors: Losman MJ,Hansen HJ,Sharkey RM,Goldenberg DM,Monestier M

    更新日期:1991-04-15 00:00:00

  • Regulation of cholesterol synthesis in rat adrenal gland through coordinate control of 3-hydroxy-3-methylglutaryl coenzyme A synthase and reductase activities.

    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

    authors: Balasubramaniam S,Goldstein JL,Brown MS

    更新日期:1977-04-01 00:00:00

  • Apoptosis and melanogenesis in human melanoma cells induced by anthrax lethal factor inactivation of mitogen-activated protein kinase kinase.

    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

    authors: Koo HM,VanBrocklin M,McWilliams MJ,Leppla SH,Duesbery NS,Vande Woude GF

    更新日期:2002-03-05 00:00:00

  • Dual regulation of NR2B and NR2C expression by NMDA receptor activation in mouse cerebellar granule cell cultures.

    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

    authors: Iijima K,Abe H,Okazawa M,Moriyoshi K,Nakanishi S

    更新日期:2008-08-19 00:00:00

  • Chemical synthesis and X-ray structure of a heterochiral {D-protein antagonist plus vascular endothelial growth factor} protein complex by racemic crystallography.

    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

    authors: Mandal K,Uppalapati M,Ault-Riché D,Kenney J,Lowitz J,Sidhu SS,Kent SB

    更新日期:2012-09-11 00:00:00

  • Mammalian sprouty proteins assemble into large monodisperse particles having the properties of intracellular nanobatteries.

    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

    authors: Wu X,Alexander PB,He Y,Kikkawa M,Vogel PD,McKnight SL

    更新日期:2005-09-27 00:00:00