Li Wai-Yee, Huang Eunice Y, Dudas Marek, Kaartinen Vesa, Warburton David, Tuan Tai-Lan
Department of Surgery, The Saban Research Institute of Childrens Hospital, Los Angeles, California 90027, USA.
Wound Repair Regen. 2006 Sep-Oct;14(5):516-25. doi: 10.1111/j.1743-6109.2006.00158.x.
For over two decades, the precise role of transforming growth factor-beta (TGF-beta) isoforms in scarless healing of mammalian fetal skin wounds has generated much interest. Although their exact role remains to be established, it has been suggested that high TGF-beta3 activity may correlate with a scarless phenotype. Previously, we showed that plasminogen activator inhibitor-1 (PAI-1), a known TGF-beta downstream molecule and marker of fibrosis, is also developmentally regulated during fetal skin development. In this study, the relationship between TGF-beta3 and PAI-1 was investigated using embryonic day 14.5 TGF-beta3 knockout (ko) mice. The results showed increased PAI-1 expression in the epidermis and dermis of ko mice, using an ex vivo limb-wounding study. Furthermore, increased PAI-1 expression and activity was seen in embryo extracts and conditioned media of ko dermal fibroblasts. When TGF-beta3 knockout fibroblasts were placed into three-dimensional collagen matrices, they were found to have decreased collagen gel contraction, suggesting altered cell-matrix interaction. These findings provide a further avenue for the interactive role of TGF-beta3 and PAI-1 during fetal scarless repair.
二十多年来，转化生长因子-β（TGF-β）亚型在哺乳动物胎儿皮肤伤口无瘢痕愈合中的精确作用引起了广泛关注。尽管它们的确切作用仍有待确定，但有人提出，高TGF-β3活性可能与无瘢痕表型相关。此前，我们发现纤溶酶原激活物抑制剂-1（PAI-1）是一种已知的TGF-β下游分子和纤维化标志物，在胎儿皮肤发育过程中也受到发育调控。在本研究中，使用胚胎第14.5天的TGF-β3基因敲除（ko）小鼠研究了TGF-β3与PAI-1之间的关系。体外肢体创伤研究结果显示，ko小鼠表皮和真皮中PAI-1表达增加。此外，在ko真皮成纤维细胞的胚胎提取物和条件培养基中，PAI-1的表达和活性也增加。当将TGF-β3基因敲除的成纤维细胞置于三维胶原基质中时，发现它们的胶原凝胶收缩能力下降，表明细胞与基质的相互作用发生了改变。这些发现为TGF-β3和PAI-1在胎儿无瘢痕修复过程中的相互作用作用提供了进一步的途径。
