Abstract:
:Pathologic ocular angiogenesis is a leading cause of blindness, influenced by both dysregulated lipid metabolism and inflammation. Retinoic-acid-receptor-related orphan receptor alpha (RORα) is a lipid-sensing nuclear receptor with diverse biologic function including regulation of lipid metabolism and inflammation; however, its role in pathologic retinal angiogenesis remains poorly understood. Using a mouse model of oxygen-induced proliferative retinopathy, we showed that RORα expression was significantly increased and genetic deficiency of RORα substantially suppressed pathologic retinal neovascularization. Loss of RORα led to decreased levels of proinflammatory cytokines and increased levels of antiinflammatory cytokines in retinopathy. RORα directly suppressed the gene transcription of suppressors of cytokine signaling 3 (SOCS3), a critical negative regulator of inflammation. Inhibition of SOCS3 abolished the antiinflammatory and vasoprotective effects of RORα deficiency in vitro and in vivo. Moreover, treatment with a RORα inverse agonist SR1001 effectively protected against pathologic neovascularization in both oxygen-induced retinopathy and another angiogenic model of very-low-density lipoprotein receptor (Vldlr)-deficient (Vldlr (-/-) ) mice with spontaneous subretinal neovascularization, whereas a RORα agonist worsened oxygen-induced retinopathy. Our data demonstrate that RORα is a novel regulator of pathologic retinal neovascularization, and RORα inhibition may represent a new way to treat ocular neovascularization.
journal_name
Proc Natl Acad Sci U S Aauthors
Sun Y,Liu CH,SanGiovanni JP,Evans LP,Tian KT,Zhang B,Stahl A,Pu WT,Kamenecka TM,Solt LA,Chen Jdoi
10.1073/pnas.1504387112subject
Has Abstractpub_date
2015-08-18 00:00:00pages
10401-6issue
33eissn
0027-8424issn
1091-6490pii
1504387112journal_volume
112pub_type
杂志文章abstract::The nuclear LIM domain protein LMO2, a T cell oncoprotein, is essential for embryonic erythropoiesis. LIM-only proteins are presumed to act primarily through protein-protein interactions. We, and others, have identified a widely expressed protein, Ldb1, whose C-terminal 76-residues are sufficient to mediate interactio...
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.94.25.13707
更新日期:1997-12-09 00:00:00
abstract::The amino acid sequence of rabbit skeletal muscle heat-stable inhibitor of the cAMP-dependent protein kinase has been determined by microsequencing techniques. Proof of the structure involved a series of nonoverlapping tryptic fragments for primary identification of 86% of the amino acids. Complementary fragments gene...
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.82.17.5732
更新日期:1985-09-01 00:00:00
abstract::The avian neuroretina (NR) is part of the central nervous system and is composed of photoreceptors, neuronal cells, and Müller (glial) cells. These cells are derived from proliferating neuroectodermal precursors that differentiate after terminal mitosis and become organized in cell strata. Genes that are specifically ...
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.88.10.4503
更新日期:1991-05-15 00:00:00
abstract::Triglyceridemic response to a standard oral fat meal was determined in 28 healthy subjects and related to the levels of several lipids, lipoproteins, and apolipoproteins in the post-absorptive plasma. A fatty test meal was administered orally, and postprandial plasma triglyceride levels were determined. In the fasting...
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.80.5.1449
更新日期:1983-03-01 00:00:00
abstract::Histone methylation has an important role in transcriptional regulation. However, unlike H3K4 and H3K9 methylation, the role of H4K20 monomethylation (H4K20me-1) in transcriptional regulation remains unclear. Here, we show that Wnt3a specifically stimulates H4K20 monomethylation at the T cell factor (TCF)-binding elem...
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.1009353108
更新日期:2011-02-22 00:00:00
abstract::The cellular alterations associated with skeletal muscle differentiation share a high degree of similarity with key phenotypic changes usually ascribed to apoptosis. For example, actin fiber disassembly/reorganization is a conserved feature of both apoptosis and differentiating myoblasts and the conserved muscle contr...
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.162172899
更新日期:2002-08-20 00:00:00
abstract::When the dog kidney Na+/K+-transporting ATPase (EC 3.6.1.37, formerly EC 3.6.1.3) was labeled with an ATP analogue, 5'-(p-fluorosulfonyl)benzoyladenosine (FSBA), there was a concomitant loss of ATPase activity. The presence of ATP protected the enzyme from both labeling and inactivation. The ATP-sensitive incorporatio...
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.83.7.2071
更新日期:1986-04-01 00:00:00
abstract::Psoralens linked to triplex-forming oligonucleotides (psoTFOs) have been used in conjunction with laser-induced two-photon excitation (TPE) to damage a specific DNA target sequence. To demonstrate that TPE can initiate photochemistry resulting in psoralen-DNA photoadducts, target DNA sequences were incubated with psoT...
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.201409698
更新日期:2001-09-25 00:00:00
abstract::Droplet manipulation is playing an important role in various fields, including scientific research, industrial production, and daily life. Here, inspired by the microstructures and functions of Namib desert beetles, Nepenthes pitcher plants, and emergent aquatic plants, we present a multibioinspired slippery surface f...
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.1912467116
更新日期:2019-10-15 00:00:00
abstract::The plant viruses alfalfa mosaic virus (AMV) and brome mosaic virus (BMV) each divide their genetic information among three RNAs while tobacco mosaic virus (TMV) contains a single genomic RNA. Amino acid sequence comparisons suggest that the single proteins encoded by AMV RNA 1 and BMV RNA 1 and by AMV RNA 2 and BMV 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.81.14.4358
更新日期:1984-07-01 00:00:00
abstract::Disruption of Rauscher leukemia virus (RLV) with low levels of Nonidet P-40 yielded "immature" cores. These cores have a diameter of about 920 A, as opposed to the 1300-A diameter of RLV, possess knob-like protuberances, and contain a concentrically coiled internal strand apposed to the core shell. The two major polyp...
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.74.8.3446
更新日期:1977-08-01 00:00:00
abstract::Photosystem I (PSI) reaction centers (RCs) of the thermophilic cyanobacterium Mastigocladus laminosus were purified and characterized. The PSI RC was obtained in two forms, monomeric and trimeric. The two forms contained the same number of pigments per P700 and displayed similar photochemical activities. The two forms...
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.88.12.5312
更新日期:1991-06-15 00:00:00
abstract::The Tsc2 gene, which is mutationally inactivated in the germ line of some families with tuberous sclerosis, encodes a large, membrane-associated GTPase activating protein (GAP) designated tuberin. Studies of the Eker rat model of hereditary cancer strongly support the role of Tsc2 as a tumor suppressor gene. In this s...
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.93.17.9154
更新日期:1996-08-20 00:00:00
abstract::Echolocating big brown bats (Eptesicus fuscus) broadcast ultrasonic frequency-modulated (FM) biosonar sounds (20-100 kHz frequencies; 10-50 microseconds periods) and perceive target range from echo delay. Knowing the acuity for delay resolution is essential to understand how bats process echoes because they perceive 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.95.21.12647
更新日期:1998-10-13 00:00:00
abstract::Helper-dependent adenoviral vectors deleted of all viral coding sequences have shown an excellent gene expression profile in a variety of animal models, as well as a reduced toxicity after systemic delivery. What is still unclear is whether long-term expression and therapeutic dosages of these vectors can be obtained ...
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.101122498
更新日期:2001-05-22 00:00:00
abstract::Although aquaporin 5 (AQP5) is the major water channel expressed in alveolar type I cells in the lung, its actual role in the lung is a matter of considerable speculation. By using immunohistochemical staining, we show that AQP5 expression in mouse lung is not restricted to type I cells, but is also detected in alveol...
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.231273398
更新日期:2001-11-20 00:00:00
abstract::The rat anterior pituitary gland (AP) receives all of its blood supply via the hypophyseal portal circulation. We now report, in rats with estradiol (E2)-induced prolactin-secreting tumors, that newly formed arteries directly supply the AP and that this arteriogenesis is closely correlated with the sensitivity of two ...
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.81.14.4549
更新日期:1984-07-01 00:00:00
abstract::An elegant expression is obtained for the product of the inverse Weierstrass-Laguerre transforms of two functions in terms of their convolution. It is also shown how the main result can be extended to hold for the product of the inverse Weierstrass-Laguerre transforms of several functions. ...
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.68.3.554
更新日期:1971-03-01 00:00:00
abstract::Event-related brain potentials (ERPs) to colored slides contained a late positive component that was significantly enhanced when adults recognized the person, place, or painting in the photograph. Additionally, two late components change in amplitude, corresponding to the amount of surprise reported. Because subjects ...
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.79.6.2121
更新日期:1982-03-01 00:00:00
abstract::Shigella sonnei is a human-adapted pathogen that is emerging globally as the dominant agent of bacterial dysentery. To investigate local establishment, we sequenced the genomes of 263 Vietnamese S. sonnei isolated over 15 y. Our data show that S. sonnei was introduced into Vietnam in the 1980s and has undergone locali...
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.1308632110
更新日期:2013-10-22 00:00:00
abstract::The formation of amyloid-like aggregates by expanded polyglutamine (polyGln) sequences is suspected to play a critical role in the neuropathology of Huntington's disease and other expanded CAG-repeat diseases. To probe the folding of the polyGln sequence in the aggregate, we replaced Gln-Gln pairs at different sequenc...
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.252523899
更新日期:2002-12-24 00:00:00
abstract::NAD(P)H:quinone oxidoreductase (NQOR; EC 1.6.99.2) is a homodimeric enzyme which catalyzes the reduction of quinones, azo dyes, and other electron acceptors by NADPH or NADH. To pursue subunit functional studies, we expressed a wild-type/mutant heterodimer of NQOR in Escherichia coli. The wild-type subunit of the hete...
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.92.4.1043
更新日期:1995-02-14 00:00:00
abstract::Delta 5-3-Ketosteroid isomerase (EC 5.3.3.1) promotes an allylic rearrangement involving intramolecular proton transfer via a dienolic intermediate. This enzyme enhances the catalytic rate by a factor of 10(10). Two residues, Tyr-14, the general acid that polarizes the steroid 3-carbonyl group and facilitates enolizat...
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.93.16.8220
更新日期:1996-08-06 00:00:00
abstract::Antibody raised against the purified human erythrocyte glucose transporter specifically precipitated four proteins from normal and Rous sarcoma virus-transformed chicken embryo cells: a major protein of Mr 41,000 and minor proteins of Mr 68,000, 73,000, and 82,000. The Mr 41,000 and 82,000 proteins were found only in ...
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.79.5.1540
更新日期:1982-03-01 00:00:00
abstract::Wild-type Escherichia coli cells grow normally in 95% O(2)/5% CO(2). In contrast, cells that cannot make polyamines because of mutations in the biosynthetic pathway are rapidly killed by incubation in 95% O(2)/5% CO(2). Addition of polyamines prevents the toxic effect of oxygen, permitting cell survival and optimal gr...
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.2627990100
更新日期:2003-03-04 00:00:00
abstract::Endometriosis is a highly prevalent gynecological disease with severe negative impacts on life quality and financial burden. Unfortunately, there is no cure for this disease, which highlights the need for further investigation about the pathophysiology of this disease to provide clues for developing novel therapeutic ...
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.1920037117
更新日期:2020-10-13 00:00:00
abstract::A high molecular weight protein (HMWP) with properties similar to those of both actin-binding protein (ABP) and filamin has been isolated from cultured baby hamster kidney (BHK-21) cells. The protein was present in an actomyosin-depleted sucrose extract of the cells and was eluted, upon gel chromatography on Sepharose...
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.76.9.4484
更新日期:1979-09-01 00:00:00
abstract::Phosphatidylionsitol 4,5-bisphosphate (PIP(2)), a substrate of phospholipase C, has recently been recognized to regulate membrane-associated proteins and act as a signal molecule in phospholipase C-linked Gq-coupled receptor (GqPCR) pathways. However, it is not known whether PIP(2) depletion induced by GqPCRs can act ...
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.0408844102
更新日期:2005-03-22 00:00:00
abstract::Water oxidation by cyanobacteria, algae, and plants is pivotal in oxygenic photosynthesis, the process that powers life on Earth, and is the paradigm for engineering solar fuel-production systems. Each complete reaction cycle of photosynthetic water oxidation requires the removal of four electrons and four protons fro...
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.1206266109
更新日期:2012-10-02 00:00:00
abstract::The chemokine CXC ligand 8 (CXCL8)/IL-8 and related agonists recruit and activate polymorphonuclear cells by binding the CXC chemokine receptor 1 (CXCR1) and CXCR2. Here we characterize the unique mode of action of a small-molecule inhibitor (Repertaxin) of CXCR1 and CXCR2. Structural and biochemical data are consiste...
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.0402090101
更新日期:2004-08-10 00:00:00