[mRNA and protein expression of three growth-related factors and their possible signal transduction pathways in wound healing].
OBJECTIVE
To observe the time course and tissue distribution of c-fos, c-myc and basic fibroblast growth factor(bFGF) genes and their proteins in burned skin, and explore the possible network regulation mechanisms of c-fos, c-myc and bFGF in wound healing and the role of the protein kinase C pathway involved in signal transduction among these growth-related factors.


METHODS
The study was carried out on 188 Wistar rats. Animal model with 30% partial thickness scald injury was made and all rats were randomly divided into several groups: normal control (n = 8), injured control (n = 36), anti-c-fos (n = 36), bFGF (n = 36), 1-5-Isoquinolinyl-sulfony-2methylpiperazine (H7), and 2, 3-Butanedione monoxime (BDM) (n = 36). In situ hybridization, reverse transcription polymerase chain reaction (RT-PCR) and streptavidin peroxidase (SP) immunohistochemistry methods were used to detect the gene and protein expression of c-fos, c-myc and bFGF in the wounded tissues.


RESULTS
(1) The first appeared induction of growth-related gene was c-fos, the second bFGF, and the last c-myc. They were peaked at 3 h, 1 d and 3 d postburn with values of 14.5 +/- 1.3, t = 13.306; 0.15 +/- 0.04, t = 3.460 and 0.11 +/- 0.05, t = 2.292, respectively (P < 0.05). (2) Treatment with c-fos antibody decreased the expression of these three growth-related factors when compared with that in the controls. There were a 80% decrease in c-myc and a 85% decrease in bFGF. (3) Treatment with H7 inhibited the gene and protein expression of c-fos and bFGF. The peak times of c-myc gene and protein were delayed to 6 hours post injury. Treatment with BDM induced an earlier expression of c-myc mRNA at 6 hours, and increased the gene and protein expressions of c-fos and bFGF. The total amount of their values was increased to 0.23 +/- 0.07, t = 2.942 and 0.69 +/- 0.07, t = 5.134 (P < 0.01).


CONCLUSIONS
Thermal injury can induce a series of growth-related gene expression showing a phasic control and regional distribution. c-fos plays an important role in wound healing process. Protein kinase C pathway may repair wound.
Fu
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X
Key Research Laboratory of Wound Repair, 304th Hospital, People's Liberation Army, Beijing 100037, China.
Gu
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X
Sun
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T
D000818:Animals; D002056:Burns / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D016762:Genes, fos; D016259:Genes, myc; D011493:Protein Kinase C / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000502:physiology; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D014945:Wound Healing
D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D011493:Protein Kinase C