Coxsackie adenovirus receptor and alpha nu beta3/alpha nu beta5 integrins in adenovirus gene transfer of rat cochlea

Autor: Venail, Frédéric, Wang, Jing, Ruel, Jérôme, Ballana, Ester, Rebillard, Guy, Eybalin, Michel, Arbones, M., Bosch, A., Puel, Jean-Luc
Přispěvatelé: Physiopathologie et thérapie des déficits sensoriels et moteurs, Université Montpellier 2 - Sciences et Techniques (UM2)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Anatomie [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Genes and Disease Program, Centre de Regulacio´ Geno´mica-CRG-UPF, Department of Biochemistry and Molecular Biology, Centre of Animal Biotechnology and Gene Therapy (CBATEG), Universitat Autònoma de Barcelona (UAB), Hamel, Christian
Jazyk: angličtina
Rok vydání: 2007
Předmět:
MESH: Integrin beta3
Integrins
Integrin beta Chains
Action Potentials
Gene Expression
MESH: Microscopy
Fluorescence

Integrin alpha5
Tissue Culture Techniques
Transduction
Genetic

MESH: Genetic Vectors
MESH: Cochlea
MESH: Integrin beta Chains
MESH: Animals
Transgenes
MESH: Action Potentials
Integrin beta3
MESH: Adenoviridae
MESH: Integrins
MESH: Transduction
Genetic

Immunohistochemistry
Cochlea
MESH: Models
Animal

Models
Animal

Receptors
Virus

[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
MESH: Integrin alpha5
Coxsackie and Adenovirus Receptor-Like Membrane Protein
MESH: Gene Expression
MESH: Rats
Genetic Vectors
Green Fluorescent Proteins
MESH: Transgenes
Adenoviridae
Injections
MESH: Green Fluorescent Proteins
otorhinolaryngologic diseases
Animals
Humans
MESH: Injections
[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
MESH: Tissue Culture Techniques
Rats
Wistar

Cochlear Nerve
MESH: Cochlear Nerve
MESH: Humans
MESH: Immunohistochemistry
Genetic Therapy
MESH: Rats
Wistar

MESH: Receptors
Virus

Rats
Microscopy
Fluorescence

MESH: Gene Therapy
Zdroj: Gene Therapy
Gene Therapy, Nature Publishing Group, 2007, 14 (1), pp.30-7. ⟨10.1038/sj.gt.3302826⟩
ISSN: 0969-7128
1476-5462
DOI: 10.1038/sj.gt.3302826⟩
Popis: International audience; This study was designed to determine whether Coxsackie adenovirus receptor (CAR) and alpha nu beta3/alpha nu beta5 integrin co-receptors are involved in adenovirus gene transfer in the rat cochlea. We find that CAR and integrin co-receptors are expressed in every cell subtype transduced by the adenoviral vector Ad5 DeltaE1-E3/cytomegalovirus/green fluorescent protein (GFP) on cochlear slices in vitro. The spiral ganglion neurons, which do not express CAR, were not transduced by the virus. Blocking these receptors by monoclonal antibodies decreased transgene expression, whereas disrupting tight junctions with ethylenediaminetetraacetic acid led to an increased transgene expression. However, sensory hair cells and strial cells also expressing CAR and alpha nu integrins were not transduced by the vector. GFP expression was also studied in vivo. Perilymphatic perfusion of adenovirus in vivo did not affect hearing and only cells lining the perilymphatic spaces were transduced. Endolymphatic perfusion resulted in low-frequency hearing loss and although some cells of the organ of Corti were efficiently transduced, the sensory and the strial cells were not. Transduced sensory and strial cells were occasionally observed in cochleas after single shot of adenovirus. Pretreatment with anti-CAR and anti-alpha nu antibodies decreases GFP expression in vivo, suggesting that the CAR/alpha nu integrin pathway is involved in adenovirus transduction in the cochlea.
Databáze: OpenAIRE