EP1407275A2 - Utilisation de facteurs de transcription nak-1 ou de genes regules par nak-1 pour le diagnostic et/ou le traitement de maladies inflammatoires et malignes - Google Patents

Utilisation de facteurs de transcription nak-1 ou de genes regules par nak-1 pour le diagnostic et/ou le traitement de maladies inflammatoires et malignes

Info

Publication number
EP1407275A2
EP1407275A2 EP02753892A EP02753892A EP1407275A2 EP 1407275 A2 EP1407275 A2 EP 1407275A2 EP 02753892 A EP02753892 A EP 02753892A EP 02753892 A EP02753892 A EP 02753892A EP 1407275 A2 EP1407275 A2 EP 1407275A2
Authority
EP
European Patent Office
Prior art keywords
nak
protein
transcription factor
pai
inflammatory
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP02753892A
Other languages
German (de)
English (en)
Inventor
Bernd R. Binder
Johannes Schmid
Johannes Bruess
Peter Hufnagl
Florian Gruber
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Instituet fur Gefassbiologie und Tromboseforschung
Original Assignee
Instituet fur Gefassbiologie und Tromboseforschung
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Instituet fur Gefassbiologie und Tromboseforschung filed Critical Instituet fur Gefassbiologie und Tromboseforschung
Publication of EP1407275A2 publication Critical patent/EP1407275A2/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6872—Intracellular protein regulatory factors and their receptors, e.g. including ion channels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6875—Nucleoproteins
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere

Definitions

  • NAK-1 transcription factor-1
  • NAK-1 transcription factor-1
  • genes regulated by NAK-1 for the diagnosis and / or therapy of inflammatory and malignant diseases
  • Transcription factors play a crucial role in inflammation in the human or animal organism. These proteins, which can bind to DNA and thus influence the regulation of their target genes, pass on information about the internal state of the cell and about the environment of the cell or factors that bind to the cell to the genes, which thereby affect these states or State changes can react.
  • NFkB A transcription factor that plays a central role in inflammatory processes is NFkB - a protein that is transported into the cell nucleus when the cell is activated by mediators of inflammation such as IL-1, TNF or LPS and can switch on "target genes". These genes contain in their control region Binding sites for NFkB; the contact of the protein with these binding sites signals that these target genes are to be produced to an increased extent, which is the cell's response to the inflammatory stimulus.
  • PAI-1 plasminogen activator inhibitor
  • PAI-1 protein is a key factor in controlling fibrin deposits in and around blood vessels. It also regulates the formation and degradation of the extracellular matrix, i.e. it is involved in plastic modifications of tissues in the area of the blood vessels. PAI-1 also plays a role in tumor processes, since PAI-1 correlates with the malignancy of tumors and is associated with the formation of metastases.
  • NAK1 is the first member of the "Nuclear Receptor Subfamily 4 / GroupA”; the homologous genes in mouse and rat are called Nur77 and NGFI-B, respectively. It was first identified as N10 by Ryseck, et al. 1989, who published it localized to human chromosome 12 (12ql3). Chang, et al. cloned it in the same year as another member of the "Steroid Receptor Superfamily" under the name TR3. Nakai et al. demonstrated in 1990 that NAK1 can be induced by serum and some mitogens and can thus be classified in the "immediate early response genes" family.
  • NAK-1 mRNA is only upregulated by bacterial toxin (LPS) if the NFKB signal transduction cascade is intact when the cells are inflamed.
  • LPS bacterial toxin
  • the inflammatory stimulus LPS stimulates the expression of NAK1 in untransfected endothelial cells and control virus-infected endothelial cells, but not of those that are transfected with IkBa and thus have no NFkB signal transduction.
  • Figure 2b shows that this mechanism is not active when NAK-1 mRNA expression is induced by TNF ⁇ . Induction cannot be inhibited by NFkB inhibitors, which indicates two inflammatory mechanisms that converge in the expression of NAK-1. It is therefore to be expected that an inhibition of the NAK-1 function as a transcriptional activator will inhibit a different spectrum of inflammatory reaction genes than an inhibition of the NFkB signal transduction pathway.
  • NAK-1 is also upregulated in humans during inflammatory events (such as atherosclerosis in this case).
  • normal and atherosclerotic vessels were stained with an antibody against NAK-1. It is found that NAK-1 is highly expressed in the atherosclerotic vessel, while the signal in the normal vessel appears to be missing (FIG. 4).
  • Fig. 4 shows a normal tissue on the left; little NAK-1 antigen is detected.
  • An atherosclerotic tissue is shown on the right in FIG. 4, the cells expressing NAK-1 antigen being darkly stained.
  • NAK-1 is only a partially NFKB-dependent transcription factor, which secondary genes, such as e.g. B. PAI-1 can turn on. Since known inhibitors of NFkB alone cannot inhibit these events, interfering with the function of NAK-1 as a transcriptional activator represents a new, expanded possibility for the treatment of inflammatory diseases and their consequences for the vascular system.
  • NAK-1 mRNA and protein expression or specific NAK-1 dependent genes By determining NAK-1 mRNA and protein expression or specific NAK-1 dependent genes, one can therefore expect to be able to detect inflammatory reactions. One can also expect to be able to modulate such inflammation reactions by influencing the NAK-1-induced transcritical ion.
  • Tumor necrosis factor increases the production of plasminogen activator inhibitor in human endothelial cells in vitro and in rats in vivo. Blood 72, 1467-1473.

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Cell Biology (AREA)
  • Pathology (AREA)
  • Food Science & Technology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • General Physics & Mathematics (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Marine Sciences & Fisheries (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Vascular Medicine (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'interaction de région promoteur PAI-1 par NAK-1 a été détectée à deux reprises par dépistage génétique. Le NAK-1 est hautement régulé par un mécanisme dépendant de NFλB dans certains types d'une réaction d'inflammation et non pas dans d'autres, NAK-1 stimulant toutefois l'expression de PAI-1 dans les deux cas. Dans la réaction d'inflammation, la régulation élevée de PAI-1 suit celle de NAK-1, et la liaison accrue NAK-1 au promoteur PAI-1 est détectable. NAK-1 est hautement régulé dans des vaisseaux athéroscléreux où PAI-1 également est fortement exprimé dans ces mêmes cellules.
EP02753892A 2001-06-27 2002-06-27 Utilisation de facteurs de transcription nak-1 ou de genes regules par nak-1 pour le diagnostic et/ou le traitement de maladies inflammatoires et malignes Withdrawn EP1407275A2 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
AT0100401A AT500019B1 (de) 2001-06-27 2001-06-27 Verwendung in vitro des transkriptionsfaktors nak-1 oder von nak-1 regulierten genen zur diagnose von entzündlichen und malignen erkrankungen
AT10042001 2001-06-27
PCT/AT2002/000188 WO2003003017A2 (fr) 2001-06-27 2002-06-27 Utilisation de facteurs de transcription nak-1 ou de genes regules par nak-1 pour le diagnostic et/ou le traitement de maladies inflammatoires et malignes

Publications (1)

Publication Number Publication Date
EP1407275A2 true EP1407275A2 (fr) 2004-04-14

Family

ID=3683976

Family Applications (1)

Application Number Title Priority Date Filing Date
EP02753892A Withdrawn EP1407275A2 (fr) 2001-06-27 2002-06-27 Utilisation de facteurs de transcription nak-1 ou de genes regules par nak-1 pour le diagnostic et/ou le traitement de maladies inflammatoires et malignes

Country Status (5)

Country Link
US (1) US20040152102A1 (fr)
EP (1) EP1407275A2 (fr)
AT (1) AT500019B1 (fr)
AU (1) AU2002322140A1 (fr)
WO (1) WO2003003017A2 (fr)

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4214215A1 (de) * 1992-04-30 1993-11-04 Behringwerke Ag Verwendung von inhibitoren von plasminogenaktivatoren zur behandlung von entzuendungen
WO1997039028A1 (fr) * 1996-04-12 1997-10-23 American National Red Cross Forme mutante de l'inhibiteur des activateurs du plasminogene du type 1 (iap-1)
US6014378A (en) * 1996-11-22 2000-01-11 Sprint Communications Company, L.P. Telecommunications tandem system for circuit-based traffic
CA2192754A1 (fr) * 1996-12-12 1998-06-12 Jacques Drouin Nur-re, element qui lie les dimeres de recepteurs nucleaires nur; methode d'obtention et utilisation
ATE346147T1 (de) * 1998-02-13 2006-12-15 Wistar Inst Zusammensetzungen und methoden zur wundheilung
AU2001229441A1 (en) * 2000-01-14 2001-07-24 Tanox, Inc. Use of antagonists of plasminogen activator inhibitor-1 (pai-1) for the treatment of asthma and chronic obstructive pulmonary disease
JP2004514649A (ja) * 2000-05-12 2004-05-20 ベイラー　カレッジ　オブ　メディシン Ｎｕｒｒサブファミリーの核転写因子の抑制による疾患に対する治療アプローチ
US20050171338A1 (en) * 2001-01-08 2005-08-04 Steven Dower Mammalian tribbles signaling pathways and methods and reagents related thereto

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO03003017A2 *

Also Published As

Publication number Publication date
AU2002322140A1 (en) 2003-03-03
WO2003003017A3 (fr) 2003-09-12
WO2003003017A2 (fr) 2003-01-09
AT500019A1 (de) 2005-10-15
US20040152102A1 (en) 2004-08-05
AT500019B1 (de) 2007-06-15

Similar Documents

Publication Publication Date Title
Capone et al. Transcriptional regulators of T helper 17 cell differentiation in health and autoimmune diseases
Ihn et al. Blockade of endogenous transforming growth factor β signaling prevents up‐regulated collagen synthesis in scleroderma fibroblasts: association with increased expression of transforming growth factor β receptors
Poulin et al. Specific protein-protein interaction between basic helix-loop-helix transcription factors and homeoproteins of the Pitx family
Farman et al. Multiple aspects of mineralocorticoid selectivity
Odermatt et al. Tissue-specific modulation of mineralocorticoid receptor function by 11β-hydroxysteroid dehydrogenases: an overview
Antoniades et al. Injury induces in vivo expression of platelet-derived growth factor (PDGF) and PDGF receptor mRNAs in skin epithelial cells and PDGF mRNA in connective tissue fibroblasts.
Charron et al. Divergent molecular mechanisms for insulin-resistant glucose transport in muscle and adipose cells in vivo.
Reichrath et al. Biologic effects of topical calcipotriol (MC 903) treatment in psoriatic skin
Ramdas et al. Glucocorticoid-induced apoptosis and regulation of NF-κB activity in human leukemic T cells
Kamitani‐Kawamoto et al. MafB interacts with Gcm2 and regulates parathyroid hormone expression and parathyroid development
Anderson et al. The molecular and biochemical basis of Duchenne muscular dystrophy
Banks et al. Characterization of human involucrin promoter distal regulatory region transcriptional activator elements–a role for Sp1 and AP1 binding sites
CH694204A5 (de) Mit dem IGF-1 Rezeptor wechselwirkende Proteine (IIPs), Nukleinsaeuren, die fuer diese codieren, und deren Verwendungen
Caputto et al. Immediate early gene expression within the visual system: light and circadian regulation in the retina and the suprachiasmatic nucleus
Werner et al. The regulation of IGF-I receptor gene expression
Wissink et al. NF-κB/Rel family members regulating the ICAM-1 promoter in monocytic THP-1 cells
Porter et al. The relationship between hyperproliferation and epidermal thickening in a mouse model for BCIE
Montani et al. Regulation of major histocompatibility class II gene expression in FRTL-5 thyrocytes: opposite effects of interferon and methimazole
Rutberg et al. CRE DNA binding proteins bind to the AP-1 target sequence and suppress AP-1 transcriptional activity in mouse keratinocytes
Kurabayashi et al. Antineoplastic agent doxorubicin inhibits myogenic differentiation of C2 myoblasts.
Suh et al. Hepatocyte nuclear factor 1 and the glucocorticoid receptor synergistically activate transcription of the rat insulin-like growth factor binding protein-1 gene
DE19957065B4 (de) Screening-Verfahren für Arzneistoffe
Montani et al. Major histocompatibility class II HLA-DRα gene expression in thyrocytes: Counter regulation by the class II transactivator and the thyroid y box protein
Suttamanatwong et al. Sp proteins and Runx2 mediate regulation of matrix gla protein (MGP) expression by parathyroid hormone
Budunova et al. Altered glucocorticoid receptor expression and function during mouse skin carcinogenesis

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE TR

AX Request for extension of the european patent

Extension state: AL LT LV MK RO SI

17P Request for examination filed

Effective date: 20040312

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20081105