| Autor: |
Du, J, Liu, L, Lay, F, Wang, Q, Dou, C, Zhang, X, Hosseini, S M, Simon, A, Rees, D J, Ahmed, A K, Sebastian, R, Sarkar, K, Milner, S, Marti, G P, Semenza, G L, Harmon, J W |
| Předmět: |
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| Zdroj: |
Gene Therapy; Nov2013, Vol. 20 Issue 11, p1070-1076, 7p |
| Abstrakt: |
Impaired burn wound healing in the elderly represents a major clinical problem. Hypoxia-inducible factor-1 (HIF-1) is a transcriptional activator that orchestrates the cellular response to hypoxia. Its actions in dermal wounds promote angiogenesis and improve healing. In a murine burn wound model, aged mice had impaired wound healing associated with reduced levels of HIF-1. When gene therapy with HIF-1 alone did not correct these deficits, we explored the potential benefit of HIF-1 gene therapy combined with the intravenous infusion of bone marrow-derived angiogenic cells (BMDACs) cultured with dimethyloxalylglycine (DMOG). DMOG is known to reduce oxidative degradation of HIF-1. The mice treated with a plasmid DNA construct expressing a stabilized mutant form of HIF-1α (CA5-HIF-1α)+BMDACs had more rapid wound closure. By day 17, there were more mice with completely closed wounds in the treated group (χ2, P=0.05). The dermal blood flow measured by laser Doppler showed significantly increased wound perfusion on day 11. Homing of BMDACs to the burn wound was dramatically enhanced by CA5-HIF-1α gene therapy. HIF-1α mRNA expression in the burn wound was increased after transfection with CA5-HIF-1α plasmid. Our findings offer insight into the pathophysiology of burns in the elderly and point to potential targets for developing new therapeutic strategies. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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