Colwell Amy S, Krummel Thomas M, Longaker Michael T, Lorenz H Peter
Department of Surgery, Division of Plastic Surgery, Children's Surgical Research Program, Stanford, Calif. 94305-5148, USA.
Plast Reconstr Surg. 2006 Jun;117(7):2297-301. doi: 10.1097/01.prs.0000218708.16909.31.
Wnt-4 is a mitogen expressed during postnatal repair and scar formation; however, its expression profile during scarless repair is unknown. Transforming growth factor (TGF)-beta1 has high expression during healing with scar formation. Whether TGF-beta1 directly influences Wnt-4 expression in fetal or postnatal fibroblasts has not been examined.
Primary fetal and postnatal mouse fibroblasts were stimulated with TGF-beta1 and Wnt-4 expression quantitated by real-time polymerase chain reaction. Fetal E17 and postnatal mouse excisional wounds were also analyzed for Wnt-4 expression by real-time polymerase chain reaction.
In E17 fibroblasts after TGF-beta1 stimulation, Wnt-4 expression increased 4-fold at 1 hour (p < 0.05) and peaked with an 11-fold increase at 2 hours (p < 0.05). By 24 hours, expression decreased to 2-fold baseline levels (p < 0.05). In postnatal fibroblasts, Wnt-4 expression also increased after TGF-beta stimulation, but peak expression was larger and relatively delayed, with a 17-fold increase at 12 hours (p < 0.005). Expression levels at 24 hours were still 4-fold greater than baseline (p < 0.05). In E17 fetal skin, Wnt-4 expression was 3.5-fold greater compared with 3-week-old mice (p < 0.005). Small increases in Wnt-4 expression (less than 2-fold) occurred during both fetal scarless and postnatal scarring mouse wound repair.
The authors' data suggest that TGF-beta directly increases Wnt-4 expression in fetal and postnatal fibroblasts and that Wnt-4 is increased in both fetal and postnatal repair.
Wnt-4是一种在出生后修复和瘢痕形成过程中表达的促有丝分裂原；然而，其在无瘢痕修复过程中的表达情况尚不清楚。转化生长因子（TGF）-β1在瘢痕形成的愈合过程中高表达。TGF-β1是否直接影响胎儿或出生后成纤维细胞中Wnt-4的表达尚未得到研究。
用TGF-β1刺激原代胎儿和出生后小鼠成纤维细胞，通过实时聚合酶链反应定量Wnt-4的表达。还通过实时聚合酶链反应分析了胎儿E17期和出生后小鼠切除伤口的Wnt-4表达。
在TGF-β1刺激后的E17期成纤维细胞中，Wnt-4表达在1小时时增加了4倍（p<0.05），并在2小时时达到峰值，增加了11倍（p<0.05）。到24小时时，表达降至基线水平的2倍（p<0.05）。在出生后成纤维细胞中，TGF-β刺激后Wnt-4表达也增加，但峰值表达更大且相对延迟，在12小时时增加了17倍（p<0.005）。24小时时的表达水平仍比基线高4倍（p<0.05）。在E17期胎儿皮肤中，Wnt-4表达比3周龄小鼠高3.5倍（p<0.005）。在胎儿无瘢痕和出生后瘢痕形成的小鼠伤口修复过程中，Wnt-4表达均有小幅增加（小于2倍）。
作者的数据表明，TGF-β直接增加胎儿和出生后成纤维细胞中Wnt-4的表达，且Wnt-4在胎儿和出生后修复过程中均增加。
