Chin G S, Lee S, Hsu M, Liu W, Kim W J, Levinson H, Longaker M T
Department of Surgery, Stanford University School of Medicine, Stanford, California, USA.
Plast Reconstr Surg. 2001 Mar;107(3):769-76. doi: 10.1097/00006534-200103000-00018.
The biochemical regulation of collagen deposition during adult cutaneous wound repair is poorly understood. Likewise, how collagen is perceived and modulated in fetal scarless healing remains unknown. Recently, discoidin domain receptors-1 and 2 (DDR1 and DDR2) with tyrosine kinase activity have been identified as novel receptors for collagen. In light of these findings, it was speculated that the production of collagen receptors DDR1 and DDR2 by fetal fibroblasts may be temporally regulated to correlate with the ontogeny of embryonic scar formation. More specifically, because DDRs directly bind collagen and transmit the signals intracellularly, it was hypothesized that they may play an important role in fetal scarless healing by ultimately regulating and modulating collagen production and organization. As part of a fundamental assessment to elucidate the role of DDRs in scarless fetal wound repair, the endogenous expression of DDR1, DDR2, collagen I, and total collagen, as a function of fetal Sprague-Dawley rat skin fibroblasts of different gestational ages, representing scar-free (<E16.5 days) and scar-forming (>E16.5) periods was determined. Using explanted dermal fibroblasts of gestational days E13.5, E16.5, E18.5, and E21.5 (term gestation = 21.5 days) fetuses (n = 92), [3H]proline incorporation assay and Northern and Western blotting analysis were performed to compare the expressions of these molecules with scar-free and scar-forming stages of embryonic development. These results revealed a pattern of increasing collagen production with increasing gestational ages, whereas DDR1 expression decreased with increasing gestational age. This observation suggests that elevated levels of DDR1 may play an important role in scarless tissue regeneration by early gestation fetal fibroblasts. In contrast, DDR2 was expressed by fetal rat fibroblasts at a similar level throughout gestation. These data demonstrate for the first time the temporal expression of collagen and DDR tyrosine kinases in fetal rat fibroblasts as a function of gestational ages. Overall, these data suggest that differential temporal expression of the above-mentioned molecules during fetal skin development may play an important role in the ontogeny of scar formation. Future studies will involve the characterization of the biomolecular functions of these receptor kinases during fetal wound repair.
在成人皮肤伤口修复过程中，胶原蛋白沉积的生化调节机制尚不清楚。同样，在胎儿无瘢痕愈合过程中，胶原蛋白是如何被感知和调节的仍然未知。最近，具有酪氨酸激酶活性的盘状结构域受体1和2（DDR1和DDR2）已被确定为胶原蛋白的新型受体。鉴于这些发现，推测胎儿成纤维细胞产生胶原蛋白受体DDR1和DDR2可能受到时间调控，以与胚胎瘢痕形成的个体发生相关。更具体地说，由于DDRs直接结合胶原蛋白并在细胞内传递信号，因此推测它们可能通过最终调节和调控胶原蛋白的产生和组织，在胎儿无瘢痕愈合中发挥重要作用。作为阐明DDRs在胎儿无瘢痕伤口修复中作用的基础评估的一部分，测定了DDR1、DDR2、I型胶原蛋白和总胶原蛋白的内源性表达，作为不同胎龄的胎儿Sprague-Dawley大鼠皮肤成纤维细胞的函数，代表无瘢痕（<E16.5天）和形成瘢痕（>E16.5）时期。使用妊娠第E13.5、E16.5、E18.5和E21.5天（足月妊娠=21.5天）胎儿的外植真皮成纤维细胞（n = 92），进行[3H]脯氨酸掺入试验以及Northern和Western印迹分析，以比较这些分子在胚胎发育的无瘢痕和形成瘢痕阶段的表达。这些结果显示随着胎龄增加胶原蛋白产生增加的模式，而DDR1表达随着胎龄增加而降低。这一观察结果表明，DDR1水平升高可能在妊娠早期胎儿成纤维细胞的无瘢痕组织再生中起重要作用。相比之下，DDR2在整个妊娠期间由胎儿大鼠成纤维细胞以相似水平表达。这些数据首次证明了胎儿大鼠成纤维细胞中胶原蛋白和DDR酪氨酸激酶的时间表达与胎龄的函数关系。总体而言，这些数据表明上述分子在胎儿皮肤发育过程中的差异时间表达可能在瘢痕形成的个体发生中起重要作用。未来的研究将涉及这些受体激酶在胎儿伤口修复过程中的生物分子功能的表征。
