title: Extracellular superoxide dismutase is a growth regulatory mediator of tissue injury recovery.
abstract: 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.
authors.affiliation: Medicity Research Laboratory, University of Turku, Turku, Finland.
authors.forename: Juha P
authors.initials: JP
authors.lastname: Laurila
authors.forename: Maria D
authors.initials: MD
authors.lastname: Castellone
authors.forename: Antonio
authors.initials: A
authors.lastname: Curcio
authors.forename: Lilja E
authors.initials: LE
authors.lastname: Laatikainen
authors.forename: Merja
authors.initials: M
authors.lastname: Haaparanta-Solin
authors.forename: Tove J
authors.initials: TJ
authors.lastname: Gronroos
authors.forename: Paivi
authors.initials: P
authors.lastname: Marjamaki
authors.forename: Satu
authors.initials: S
authors.lastname: Martikainen
authors.forename: Massimo
authors.initials: M
authors.lastname: Santoro
authors.forename: Mikko O
authors.initials: MO
authors.lastname: Laukkanen
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005110:Extracellular Space / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000378:metabolism; D006614:Hindlimb / Q000201:enzymology* / Q000293:injuries / Q000473:pathology*; D006801:Humans; D007511:Ischemia / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D020935:MAP Kinase Signaling System; D008297:Male; D011817:Rabbits; D051381:Rats; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics; D018631:ras Proteins / Q000378:metabolism
chemical_list: D013482:Superoxide Dismutase; D048049:Extracellular Signal-Regulated MAP Kinases; D018631:ras Proteins; D005947:Glucose