Stelnicki E J, Arbeit J, Cass D L, Saner C, Harrison M, Largman C
Department of Surgery, University of California, San Francisco, USA.
J Invest Dermatol. 1998 Jul;111(1):57-63. doi: 10.1046/j.1523-1747.1998.00238.x.
Scarless healing of cutaneous wounds occurs in humans during the first two trimesters of development, but by birth all wounds are repaired with scar formation. To search for transcriptional regulatory genes that might mediate fetal tissue regeneration, we surveyed homeobox gene expression in proliferating fetal fibroblasts and in wounded and unwounded skin. Two novel human homeobox genes, PRX-2 and HOXB13, were identified that were differentially expressed during fetal versus adult wound healing. Both genes were predominantly expressed in proliferating fetal fibroblasts and developing dermis, and PRX-2 was downregulated in adult skin. In a model of scarless fetal skin regeneration, PRX-2 expression was strongly increased compared with unwounded skin and the signal was localized to the wounded dermis, the site of scarless repair. Conversely, in adult skin weak epidermal PRX-2 expression was observed, mRNA levels were not increased by wounding, and no dermal expression was detected. HOXB13 expression was decreased in wounded fetal tissue relative to unwounded fetal controls or wounded adult skin. Thus both HOXB13 and PRX-2 are expressed in patterns consistent with roles in fetal skin development and cutaneous regeneration.
人类皮肤伤口在发育的前两个阶段可实现无瘢痕愈合，但出生时所有伤口均通过瘢痕形成来修复。为了寻找可能介导胎儿组织再生的转录调控基因，我们研究了增殖期胎儿成纤维细胞以及受伤和未受伤皮肤中的同源框基因表达情况。我们鉴定出两个新的人类同源框基因PRX - 2和HOXB13，它们在胎儿与成人伤口愈合过程中表达存在差异。这两个基因主要在增殖期胎儿成纤维细胞和发育中的真皮中表达，并且PRX - 2在成人皮肤中表达下调。在无瘢痕胎儿皮肤再生模型中，与未受伤皮肤相比，PRX - 2的表达显著增加，且信号定位于伤口真皮层，即无瘢痕修复的部位。相反，在成人皮肤中观察到PRX - 2在表皮中的微弱表达，受伤后mRNA水平未升高，且未检测到真皮层表达。与未受伤的胎儿对照或受伤的成人皮肤相比，HOXB13在受伤的胎儿组织中表达降低。因此，HOXB13和PRX - 2的表达模式均与它们在胎儿皮肤发育和皮肤再生中的作用相符。
