P53 EXPRESSION DURING NORMAL TISSUE REGENERATION IN RESPONSE TO ACUTECUTANEOUS INJURY IN SWINE

The present studies investigated the in vivo expression of the p53 sup pressor gene and protein product in response to acute cutaneous injury in swine, along with the parallel expression of the c-sis/PDGF-B mito gen and its receptor beta (PDGF-R beta). p53 expression was shown to b e suppressed during the period of active cellular proliferation in the injured tissue and to reemerge during the stages of healing. In contr ast, c-sis/PDGF-B and PDGF-R beta were expressed during the early phas e of active cellular proliferation and they were suppressed upon heali ng. This inverse relationship between mitogenic growth factors and p53 suggests the presence of well-controlled physiologic mechanisms that regulate in vivo the processes of normal tissue repair in response to injury. At the stages of tissue regeneration, these mechanisms include both the expression of growth factors that promote cell proliferation and the suppression of p53 that downregulates proliferation. At the s tages of healing, the expression of the mitogenic growth factors is su ppressed and that of p53 reemerges, reaching its peak at the time of c omplete epithelialization and healing of the injured tissue. These stu dies are the first to link the response of p53 protein to physiologic processes of tissue regeneration in vivo.