Preventing local regeneration of glucocorticoids by 11beta-hydroxysteroid dehydrogenase type 1 enhances angiogenesis.

Abstract:

:Angiogenesis restores blood flow to healing tissues, a process that is inhibited by high doses of glucocorticoids. However, the role of endogenous glucocorticoids and the potential for antiglucocorticoid therapy to enhance angiogenesis is unknown. Using in vitro and in vivo models of angiogenesis in mice, we examined effects of (i) endogenous glucocorticoids, (ii) blocking endogenous glucocorticoid action with the glucocorticoid receptor antagonist RU38486, and (iii) abolishing local regeneration of glucocorticoids by the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1). Glucocorticoids, administered at physiological concentrations, inhibited angiogenesis in an in vitro aortic ring model and in vivo in polyurethane sponges implanted s.c. RU38486-enhanced angiogenesis in s.c. sponges, in healing surgical wounds, and in the myocardium of mice 7 days after myocardial infarction induced by coronary artery ligation. 11betaHSD1 knockout mice showed enhanced angiogenesis in vitro and in vivo within sponges, wounds, and infarcted myocardium. Endogenous glucocorticoids, including those generated locally by 11betaHSD1, exert tonic inhibition of angiogenesis. Inhibition of 11betaHSD1 in liver and adipose has been advocated to reduce cardiovascular risk in the metabolic syndrome: these data suggest that 11betaHSD1 inhibition offers a previously uncharacterized therapeutic approach to improve healing of ischemic or injured tissue.

authors

Small GR,Hadoke PW,Sharif I,Dover AR,Armour D,Kenyon CJ,Gray GA,Walker BR

doi

10.1073/pnas.0500641102

keywords:

subject

Has Abstract

pub_date

2005-08-23 00:00:00

pages

12165-70

issue

34

eissn

0027-8424

issn

1091-6490

pii

0500641102

journal_volume

102

pub_type

杂志文章
  • Song presentation induces gene expression in the songbird forebrain.

    abstract::We investigated the participation of genomic regulatory events in the response of the songbird brain to a natural auditory stimulus of known physiological and behavioral relevance, birdsong. Using in situ hybridization, we detected a rapid increase in forebrain mRNA levels of an immediate-early gene encoding a transcr...

    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.89.15.6818

    authors: Mello CV,Vicario DS,Clayton DF

    更新日期:1992-08-01 00:00:00

  • The identification of an osteoclastogenesis inhibitor through the inhibition of glyoxalase I.

    abstract::Osteoclasts, bone-resorptive multinucleated cells derived from hematopoietic stem cells, are associated with many bone-related diseases, such as osteoporosis. Osteoclast-targeting small-molecule inhibitors are valuable tools for studying osteoclast biology and for developing antiresorptive agents. Here, we have discov...

    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.0712239105

    authors: Kawatani M,Okumura H,Honda K,Kanoh N,Muroi M,Dohmae N,Takami M,Kitagawa M,Futamura Y,Imoto M,Osada H

    更新日期:2008-08-19 00:00:00

  • The effect of gene interactions on the long-term response to selection.

    abstract::The role of gene interactions in the evolutionary process has long been controversial. Although some argue that they are not of importance, because most variation is additive, others claim that their effect in the long term can be substantial. Here, we focus on the long-term effects of genetic interactions under direc...

    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.1518830113

    authors: Paixão T,Barton NH

    更新日期:2016-04-19 00:00:00

  • Inhibition of ErbB3 by a monoclonal antibody that locks the extracellular domain in an inactive configuration.

    abstract::ErbB3 (HER3) is a member of the EGF receptor (EGFR) family of receptor tyrosine kinases, which, unlike the other three family members, contains a pseudo kinase in place of a tyrosine kinase domain. In cancer, ErbB3 activation is driven by a ligand-dependent mechanism through the formation of heterodimers with EGFR, Er...

    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.1518361112

    authors: Lee S,Greenlee EB,Amick JR,Ligon GF,Lillquist JS,Natoli EJ Jr,Hadari Y,Alvarado D,Schlessinger J

    更新日期:2015-10-27 00:00:00

  • Low levels of deoxynucleotides in peripheral blood lymphocytes: a strategy to inhibit human immunodeficiency virus type 1 replication.

    abstract::Human immunodeficiency virus type 1 (HIV-1) viral DNA synthesis in quiescent and activated peripheral blood lymphocytes (PBLs) was studied. Incomplete viral DNA (previously demonstrated to be associated with HIV-1 virions) is carried by HIV-1 virions into quiescent and activated PBLs, contributing to the formation of ...

    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.90.19.8925

    authors: Gao WY,Cara A,Gallo RC,Lori F

    更新日期:1993-10-01 00:00:00

  • Modulation by gangliosides of the lamellar-inverted micelle (hexagonal II) phase transition in mixtures containing phosphatidylethanolamine and dioleoylglycerol.

    abstract::We studied the effect of gangliosides GD1a and GM1 on the lamellar-to-hexagonal II phase transition of mixtures of dioleoylphosphatidylethanolamine/dioleoylphosphatidyl choline, 3:1, and of transphosphatidylated phosphatidylethanolamine with dioleoylglycerol by high-sensitivity differential scanning calorimetry, 31P-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.91.21.10019

    authors: Perillo MA,Scarsdale NJ,Yu RK,Maggio B

    更新日期:1994-10-11 00:00:00

  • p85α deficiency protects β-cells from endoplasmic reticulum stress-induced apoptosis.

    abstract::In insulin resistant states such as type 2 diabetes, there is a high demand on the β-cell to synthesize and secrete insulin, which challenges the ability of the endoplasmic reticulum (ER) to synthesize and fold nascent proteins. This creates a state of ER stress that triggers a coordinated program referred to as the u...

    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.1322564111

    authors: Winnay JN,Dirice E,Liew CW,Kulkarni RN,Kahn CR

    更新日期:2014-01-21 00:00:00

  • Cytoskeletal reorganizations responsible for the phorbol ester-induced formation of cytoplasmic processes: possible involvement of intermediate filaments.

    abstract::The tumor promoter phorbol 12-myristate 13-acetate (PMA) induces characteristic reversible changes of cell shape in certain fibroblastic lines: motile lamellas are transformed into noncontractile narrow processes; simultaneously, the actin microfilament network of lamellas is locally disorganized. This reaction to PMA...

    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.87.5.1884

    authors: Bershadsky AD,Ivanova OY,Lyass LA,Pletyushkina OY,Vasiliev JM,Gelfand IM

    更新日期:1990-03-01 00:00:00

  • Temporal association of elevated cholecystokininergic tone and adolescent trauma is critical for posttraumatic stress disorder-like behavior in adult mice.

    abstract::Adolescent trauma (AT) is a common risk factor for adult-onset posttraumatic stress disorder (PTSD). However, the vulnerability to AT among different individuals varies dramatically, indicating that other cofactors are important. Despite extensive studies, the identification of those cofactors has had little success. ...

    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.1219601110

    authors: Joseph A,Tang M,Mamiya T,Chen Q,Yang LL,Jiao J,Yu N,Tang YP

    更新日期:2013-04-16 00:00:00

  • Analysis of 13 cell types reveals evidence for the expression of numerous novel primate- and tissue-specific microRNAs.

    abstract::Two decades after the discovery of the first animal microRNA (miRNA), the number of miRNAs in animal genomes remains a vexing question. Here, we report findings from analyzing 1,323 short RNA sequencing samples (RNA-seq) from 13 different human tissue types. Using stringent thresholding criteria, we identified 3,707 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.1420955112

    authors: Londin E,Loher P,Telonis AG,Quann K,Clark P,Jing Y,Hatzimichael E,Kirino Y,Honda S,Lally M,Ramratnam B,Comstock CE,Knudsen KE,Gomella L,Spaeth GL,Hark L,Katz LJ,Witkiewicz A,Rostami A,Jimenez SA,Hollingsworth MA,

    更新日期:2015-03-10 00:00:00

  • Mutational analysis of protein phosphatase 2C involved in abscisic acid signal transduction in higher plants.

    abstract::Protein phosphatase 2C (PP2C) is a class of ubiquitous and evolutionarily conserved serine/threonine PP involved in stress responses in yeasts, mammals, and plants. Here, I present mutational analysis of two Arabidopsis thaliana PP2Cs, encoded by ABI1 and AtPP2C, involved in the plant stress hormone abscisic acid (ABA...

    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.95.3.975

    authors: Sheen J

    更新日期:1998-02-03 00:00:00

  • Inhibition of human natural killer cell activity by (14R,15S)-14,15-dihydroxy-5Z,8Z,10E,12E- icosatetraenoic acid.

    abstract::The interactions between products of the 15-lipoxygenase cascade and human natural killer (NK) cell activity have been studied. Addition of human leukocyte-derived (14R,15S)-14,15-dihydroxy-5Z,8Z,10E,12E-ic osatetraenoic acid (14,15-DiHETE) to the NK cytotoxicity assay against K562 target cells resulted in inhibition ...

    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.81.22.6914

    authors: Ramstedt U,Serhan CN,Lundberg U,Wigzell H,Samuelsson B

    更新日期:1984-11-01 00:00:00

  • Analysis of perinatal gene expression: hormone response elements mediate activation of a lacZ reporter gene in liver of transgenic mice.

    abstract::The transcription of genes encoding gluconeogenic enzymes is tightly regulated during the perinatal period. These genes are induced by glucagon (cAMP) and glucocorticoids and repressed by insulin. To address the role of cAMP and glucocorticoids in the physiological activation of genes encoding gluconeogenic enzymes 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.92.10.4244

    authors: Montoliu L,Blendy JA,Cole TJ,Schütz G

    更新日期:1995-05-09 00:00:00

  • Protection of cardiac mitochondria by diazoxide and protein kinase C: implications for ischemic preconditioning.

    abstract::Mitochondrial ATP-sensitive K (mitoK(ATP)) channels play a central role in protecting the heart from injury in ischemic preconditioning. In isolated mitochondria exposed to elevated extramitochondrial Ca, P(i), and anoxia to simulate ischemic conditions, the selective mitoK(ATP) channel agonist diazoxide (25-50 microM...

    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.052713199

    authors: Korge P,Honda HM,Weiss JN

    更新日期:2002-03-05 00:00:00

  • Misfolded CuZnSOD and amyotrophic lateral sclerosis.

    abstract::Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disease of motor neurons. The inherited form of the disease, familial ALS, represents 5-10% of the total cases, and the best documented of these are due to lesions in SOD1, the gene encoding copper-zinc superoxide dismutase (CuZnSOD). The mechanism by w...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章,评审

    doi:10.1073/pnas.0730423100

    authors: Valentine JS,Hart PJ

    更新日期:2003-04-01 00:00:00

  • Survival without recovery after mass extinctions.

    abstract::Because many survivors of mass extinctions do not participate in postrecovery diversifications, and therefore fall into a pattern that can be termed "Dead Clade Walking" (DCW), the effects of mass extinctions extend beyond the losses observed during the event itself. Analyses at two taxonomic levels provide a first-or...

    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.102163299

    authors: Jablonski D

    更新日期:2002-06-11 00:00:00

  • A lymphocyte antigen encoded by a locus closely linked to H-3 on the second chromosome of the mouse.

    abstract::A monoclonal antibody has been developed that recognizes a mouse lymphocyte antigen, Ly-23, that is controlled by an H-3 histocompatibility complex-linked gene on the second chromosome. Competitive binding experiments demonstrate that this antigen is distinct from the polymorphic beta 2-microglobulin antigen, which al...

    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.80.21.6620

    authors: Gasser DL,Ziebur J,Matsumoto K

    更新日期:1983-11-01 00:00:00

  • Acetylcholine receptor-alpha-bungarotoxin interactions: determination of the region-to-region contacts by peptide-peptide interactions and molecular modeling of the receptor cavity.

    abstract::In previous studies from this laboratory, the binding regions of alpha-neurotoxins on human and Torpedo acetylcholine (AcCho) receptors (AcChoRs) and the binding regions for the receptor on the toxin were characterized with synthetic peptides of the respective molecules. In the present work, peptides representing 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.87.16.6156

    authors: Ruan KH,Spurlino J,Quiocho FA,Atassi MZ

    更新日期:1990-08-01 00:00:00

  • Rhythms of Drosophila period gene expression in culture.

    abstract::The Drosophila clock genes period (per) and timeless (tim) have been studied behaviorally and biochemically, but to date there has been no viable culture system for studying the cell biology of the Drosophila clock. We have cultured pupal ring glands attached to the central nervous system and observed rhythms of perio...

    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.94.8.4092

    authors: Emery IF,Noveral JM,Jamison CF,Siwicki KK

    更新日期:1997-04-15 00:00:00

  • GA-binding protein factors, in concert with the coactivator CREB binding protein/p300, control the induction of the interleukin 16 promoter in T lymphocytes.

    abstract::Interleukin 16 (IL-16) is a chemotactic cytokine that binds to the CD4 receptor and affects the activation of T cells and replication of HIV. It is expressed as a large 67-kDa precursor protein (pro-IL-16) in lymphocytes, macrophages, and mast cells, as well as in airway epithelial cells from asthmatics after challeng...

    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.96.4.1541

    authors: Bannert N,Avots A,Baier M,Serfling E,Kurth R

    更新日期:1999-02-16 00:00:00

  • Sustained representation of perspectival shape.

    abstract::Arguably the most foundational principle in perception research is that our experience of the world goes beyond the retinal image; we perceive the distal environment itself, not the proximal stimulation it causes. Shape may be the paradigm case of such "unconscious inference": When a coin is rotated in depth, we infer...

    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.2000715117

    authors: Morales J,Bax A,Firestone C

    更新日期:2020-06-30 00:00:00

  • Direct high-resolution mapping of electrocatalytic activity of semi-two-dimensional catalysts with single-edge sensitivity.

    abstract::The catalytic activity of low-dimensional electrocatalysts is highly dependent on their local atomic structures, particularly those less-coordinated sites found at edges and corners; therefore, a direct probe of the electrocatalytic current at specified local sites with true nanoscopic resolution has become critically...

    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.1821091116

    authors: Sun T,Wang D,Mirkin MV,Cheng H,Zheng JC,Richards RM,Lin F,Xin HL

    更新日期:2019-06-11 00:00:00

  • Antibody recognition of a unique tumor-specific glycopeptide antigen.

    abstract::Aberrant glycosylation and the overexpression of certain carbohydrate moieties is a consistent feature of cancers, and tumor-associated oligosaccharides are actively investigated as targets for immunotherapy. One of the most common aberrations in glycosylation patterns is the presentation of a single O-linked N-acetyl...

    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.0915176107

    authors: Brooks CL,Schietinger A,Borisova SN,Kufer P,Okon M,Hirama T,Mackenzie CR,Wang LX,Schreiber H,Evans SV

    更新日期:2010-06-01 00:00:00

  • Label-free and charge-sensitive dynamic imaging of lipid membrane hydration on millisecond time scales.

    abstract::Biological membranes are highly dynamic and complex lipid bilayers, responsible for the fate of living cells. To achieve this function, the hydrating environment is crucial. However, membrane imaging typically neglects water, focusing on the insertion of probes, resonant responses of lipids, or the hydrophobic core. O...

    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.1719347115

    authors: Tarun OB,Hannesschläger C,Pohl P,Roke S

    更新日期:2018-04-17 00:00:00

  • Activation of the epsilon isoform of protein kinase C in the mammalian nerve terminal.

    abstract::Activation of protein kinase C (PKC) by phorbol ester facilitates hormonal secretion and transmitter release, and phorbol ester-induced synaptic potentiation (PESP) is a model for presynaptic facilitation. A variety of PKC isoforms are expressed in the central nervous system, but the isoform involved in the PESP has 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.241333598

    authors: Saitoh N,Hori T,Takahashi T

    更新日期:2001-11-20 00:00:00

  • The IL-6- and lipopolysaccharide-induced transcription of hepcidin in HFE-, transferrin receptor 2-, and beta 2-microglobulin-deficient hepatocytes.

    abstract::The antimicrobial peptide hepcidin appears to play a central role in the regulation of iron homeostasis. In intact animals, iron overload or the injection of lipopolysaccharide (LPS) stimulates transcription of HAMP, the gene that encodes hepcidin. In isolated hepatocytes, IL-6, an inflammatory cytokine the production...

    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.0403108101

    authors: Lee P,Peng H,Gelbart T,Beutler E

    更新日期:2004-06-22 00:00:00

  • Global trends in nature's contributions to people.

    abstract::Declining biodiversity and ecosystem functions put many of nature's contributions to people at risk. We review and synthesize the scientific literature to assess 50-y global trends across a broad range of nature's contributions. We distinguish among trends in potential and realized contributions of nature, as well as ...

    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.2010473117

    authors: Brauman KA,Garibaldi LA,Polasky S,Aumeeruddy-Thomas Y,Brancalion PHS,DeClerck F,Jacob U,Mastrangelo ME,Nkongolo NV,Palang H,Pérez-Méndez N,Shannon LJ,Shrestha UB,Strombom E,Verma M

    更新日期:2020-12-22 00:00:00

  • Distinguishing surface effects of calcium ion from pore-occupancy effects in Na+ channels.

    abstract::The effects of calcium ion on the Na+ activation gate were studied in squid giant axons. Saxitoxin (STX) was used to block ion entry into Na+ channels without hindering access to the membrane surface, making it possible to distinguish surface effects of calcium from pore-occupancy effects. In the presence of STX, gati...

    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.96.7.4158

    authors: Armstrong CM

    更新日期:1999-03-30 00:00:00

  • Homology of lipoprotein lipase to pancreatic lipase.

    abstract::Bovine milk lipoprotein lipase was subjected to amino acid sequence analysis. The first 19 amino-terminal residues were Asp-Arg-Ile-Thr-Gly-Gly-Lys-Asp-Phe-Arg-Asp-Ile-Glu-Ser-Lys-Phe-Ala-Leu- Arg. In addition, reversed-phase high-performance liquid chromatography of a tryptic digest of reduced and alkylated lipase re...

    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.83.12.4185

    authors: Ben-Avram CM,Ben-Zeev O,Lee TD,Haaga K,Shively JE,Goers J,Pedersen ME,Reeve JR Jr,Schotz MC

    更新日期:1986-06-01 00:00:00

  • Characterization of inhibitory and stimulatory forms of the murine natural killer cell receptor 2B4.

    abstract::The receptor 2B4 belongs to the Ig superfamily and is found on the surface of all murine natural killer (NK) cells as well as T cells displaying non-MHC-restricted cytotoxicity. Previous studies have suggested that 2B4 is an activating molecule because cross-linking of this receptor results in increased cytotoxicity 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.96.7.3870

    authors: Schatzle JD,Sheu S,Stepp SE,Mathew PA,Bennett M,Kumar V

    更新日期:1999-03-30 00:00:00