Genomic analysis of insulin-like growth factor-I gene transfer in thermally injured rats.
Thermal trauma causes tissue damage by membrane destabilization and energy depletion at the cellular level, resulting in tissue necrosis and inflammation leading to delayed cell death. One therapeutic approach is to block the immediate triggering of the inflammatory cascade that results in prolonged hypermetabolic responses and immune dysfunction while promoting the expression of growth factors. In the present study, we determined hepatic gene expression responses to insulin-like growth factors-i (IGF-I) gene transfer to burned rats using high-density DNA microarray assays. The expression of 123 out of approximately 8,800 genes assayed (1.4% of total) were significantly altered. Of these, 42 genes were altered irrespective of treatment by burn trauma (p < 0.05). Changes in gene expression were confirmed by measuring mRNA levels using reverse transcription-polymerase chain reaction and protein levels by Western blot assays. DNA microarray analyses showed two major mechanisms that mediated beneficial outcomes after IGF-I gene transfer in the burned rat livers. These mechanisms were the stimulation of IGF binding protein potentiation of peripheral IGF-I and the inhibition of the burn-augmented pro-apoptotic and oxidative mitochondrial metabolites stimulated by thermal trauma.
Dasu
Mohan R K
MR
Shriners Hospitals for Children, and Department of Surgery, The University of Texas Medical Branch, Galveston, Texas 77550, USA. drmohan@utmb.edu
Herndon
David N
DN
Spies
Marcus
M
Perez-Polo
J Regino
JR
D000818:Animals; D002056:Burns / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051766:Early Growth Response Protein 1; D018014:Gene Transfer Techniques; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D019679:Kininogen, High-Molecular-Weight / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D018075:RNA, Complementary / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D019679:Kininogen, High-Molecular-Weight; D018075:RNA, Complementary; D012333:RNA, Messenger; D014157:Transcription Factors; D007334:Insulin-Like Growth Factor I