ß cell protection by inhibition of iNOS through lentiviral vector-based strategies.
Methods Mol Biol
; 704: 153-68, 2011.
Article
em En
| MEDLINE
| ID: mdl-21161636
ABSTRACT
Cytoprotective gene transfer to pancreatic islet ß cell s may prove useful in preventing their destruction and prolonging islet graft survival after transplantation in patients with type 1 diabetes mellitus. A host of therapeutically relevant transgenes may potentially be incorporated into an appropriate gene delivery vehicle and used for islet modification. To examine this, we utilised a robust model of cytokine-induced ß cell pathophysiology. Using this model, it is clear that antioxidant gene transfer confers no cytoprotective benefit. In contrast, we demonstrated that gene-based approaches to inhibit the activation of NF-κBNF-κB following cytokine exposure harbours therapeutic utility in preserving islet ß cell viability in the face of cytokine toxicity. We identified that NF-κB-dependent induction of iNOSiNOS is a critical determinant of ß cell fate following cytokine exposure. Having identified the pivotal role of iNOS activation in cytokine-induced ß cell pathophysiology, lentiviral vectors may be used to efficiently deliver small interfering RNARNA molecules to confer efficient iNOS gene silencing. We have shown that lentiviral vector-based shRNA delivery holds significant promise in preserving ß cell viability following cytotoxic cytokine exposure.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Terapia Genética
/
Lentivirus
/
Citoproteção
/
Células Secretoras de Insulina
/
Óxido Nítrico Sintase Tipo II
/
Vetores Genéticos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Methods Mol Biol
Ano de publicação:
2011
Tipo de documento:
Article