Mack Judith A, Abramson Susan R, Ben Yixen, Coffin Jerusha C, Rothrock James K, Maytin Edward V, Hascall Vincent C, Largman Corey, Stelnicki Eric J
Department of Research, Cleveland Clinic Florida, Weston, Florida, USA.
FASEB J. 2003 Jul;17(10):1352-4. doi: 10.1096/fj.02-0959fje. Epub 2003 May 20.
In contrast to adult cutaneous wound repair, early gestational fetal cutaneous wounds heal by a process of regeneration, resulting in little or no scarring. Previous studies indicate that down-regulation of HoxB13, a member of the highly conserved family of Hox transcription factors, occurs during fetal scarless wound healing. No down-regulation was noted in adult wounds. Here, we evaluate healing of adult cutaneous wounds in Hoxb13 knockout (KO) mice, hypothesizing that loss of Hoxb13 in adult skin should result in enhanced wound healing. Tensiometry was used to measure the tensile strength of incisional wounds over a 60-day time course; overall, Hoxb13 KO wounds are significantly stronger than wild-type (WT). Histological evaluation of incisional wounds shows that 7-day-old Hoxb13 KO wounds are significantly smaller and that 60-day-old Hoxb13 KO wounds exhibit a more normal collagen architecture compared with WT wounds. We also find that excisional wounds close at a faster rate in Hoxb13 KO mice. Biochemical and histochemical analyses show that Hoxb13 KO skin contains significantly elevated levels of hyaluronan. Because higher levels of hyaluronan and enhanced wound healing are characteristics of fetal skin, we conclude that loss of Hoxb13 produces a more "fetal-like" state in adult skin.
与成人皮肤伤口修复不同，妊娠早期胎儿皮肤伤口通过再生过程愈合，几乎不会留下疤痕。先前的研究表明，在胎儿无疤痕伤口愈合过程中，高度保守的Hox转录因子家族成员HoxB13的表达下调。在成人伤口中未观察到这种下调。在此，我们评估了Hoxb13基因敲除（KO）小鼠的成人皮肤伤口愈合情况，假设成人皮肤中Hoxb13的缺失应会增强伤口愈合。在60天的时间进程中，使用张力测定法测量切口伤口的抗张强度；总体而言，Hoxb13基因敲除伤口比野生型（WT）伤口明显更强。对切口伤口的组织学评估表明，7日龄的Hoxb13基因敲除伤口明显更小，与野生型伤口相比，60日龄的Hoxb13基因敲除伤口显示出更正常的胶原结构。我们还发现，在Hoxb13基因敲除小鼠中，切除伤口的闭合速度更快。生化和组织化学分析表明，Hoxb13基因敲除皮肤中透明质酸水平显著升高。由于较高水平的透明质酸和增强的伤口愈合是胎儿皮肤的特征，我们得出结论，Hoxb13的缺失在成人皮肤中产生了更“类似胎儿”的状态。
