Antoniades H N, Galanopoulos T, Neville-Golden J, Kiritsy C P, Lynch S E
Center for Blood Research, Boston, Massachusetts.
J Clin Invest. 1994 May;93(5):2206-14. doi: 10.1172/JCI117217.
The present studies investigated the in vivo expression of the p53 suppressor gene and protein product in response to acute cutaneous injury in swine, along with the parallel expression of the c-sis/PDGF-B mitogen and its receptor beta (PDGF-R beta). p53 expression was shown to be suppressed during the period of active cellular proliferation in the injured tissue and to reemerge during the stages of healing. In contrast, c-sis/PDGF-B and PDGF-R beta were expressed during the early phase of active cellular proliferation and they were suppressed upon healing. 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 stages of healing, the expression of the mitogenic growth factors is suppressed and that of p53 reemerges, reaching its peak at the time of complete epithelialization and healing of the injured tissue. These studies are the first to link the response of p53 protein to physiologic processes of tissue regeneration in vivo.
本研究调查了猪急性皮肤损伤后p53抑癌基因及其蛋白产物的体内表达情况,以及c-sis/血小板衍生生长因子B(PDGF-B)有丝分裂原及其受体β(PDGF-Rβ)的平行表达情况。结果显示,在损伤组织的活跃细胞增殖期,p53表达受到抑制,而在愈合阶段重新出现。相反,c-sis/PDGF-B和PDGF-Rβ在活跃细胞增殖的早期阶段表达,愈合时受到抑制。有丝分裂生长因子与p53之间的这种反向关系表明,存在调控体内正常组织损伤修复过程的严格生理机制。在组织再生阶段,这些机制包括促进细胞增殖的生长因子的表达以及下调增殖的p53的抑制。在愈合阶段,有丝分裂生长因子的表达受到抑制,p53的表达重新出现,在损伤组织完全上皮化和愈合时达到峰值。这些研究首次将p53蛋白的反应与体内组织再生的生理过程联系起来。