A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Extracellular Superoxide Dismutase Is a Growth Regulatory Mediator of Tissue Injury Recovery
Tekijät: Laurila JP, Castellone MD, Curcio A, Laatikainen LE, Haaparanta-Solin M, Gronroos TJ, Marjamaki P, Martikainen S, Santoro M, Laukkanen MO
Kustantaja: NATURE PUBLISHING GROUP
Julkaisuvuosi: 2009
Journal: Molecular Therapy
Tietokannassa oleva lehden nimi: MOLECULAR THERAPY
Lehden akronyymi: MOL THER
Vuosikerta: 17
Numero: 3
Aloitussivu: 448
Lopetussivu: 454
Sivujen määrä: 7
ISSN: 1525-0016
DOI: https://doi.org/10.1038/mt.2008.282
Tiivistelmä
Extracellular superoxide dismutase (SOD3) gene therapy has been shown to attenuate tissue damages and to improve the recovery of the tissue injuries, but the cellular events delivering the therapeutic response of the enzyme are not well defined. In the current work, we overexpressed SOD3 in rat hindlimb ischemia model to study the signal transduction and injury healing following the sod3 gene transfer. The data suggest a novel sod3 gene transfer-derived signal transduction cascade through Ras-Mek-Erk mitogenic pathway leading to activation of AP1 and CRE transcription factors, increased vascular endothelial growth factor (VEGF)-A and cyclin D1 expression, increased cell proliferation, and consequently improved metabolic functionality of the injured tissue. Increased cell proliferation could explain the improved metabolic performance and the healing of the tissue damages after the sod3 gene transfer. The present data is a novel description of the molecular mechanism of SOD3-mediated recovery of tissue injury and suggests a new physiological role for SOD3 as a Ras regulatory molecule in signal transduction.
Extracellular superoxide dismutase (SOD3) gene therapy has been shown to attenuate tissue damages and to improve the recovery of the tissue injuries, but the cellular events delivering the therapeutic response of the enzyme are not well defined. In the current work, we overexpressed SOD3 in rat hindlimb ischemia model to study the signal transduction and injury healing following the sod3 gene transfer. The data suggest a novel sod3 gene transfer-derived signal transduction cascade through Ras-Mek-Erk mitogenic pathway leading to activation of AP1 and CRE transcription factors, increased vascular endothelial growth factor (VEGF)-A and cyclin D1 expression, increased cell proliferation, and consequently improved metabolic functionality of the injured tissue. Increased cell proliferation could explain the improved metabolic performance and the healing of the tissue damages after the sod3 gene transfer. The present data is a novel description of the molecular mechanism of SOD3-mediated recovery of tissue injury and suggests a new physiological role for SOD3 as a Ras regulatory molecule in signal transduction.
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