Yeh Jennifer, Green Lydia M, Jiang Ting-Xin, Plikus Maksim, Huang Eunice, Chang Richard N, Hughes Michael W, Chuong Cheng-Ming, Tuan Tai-Lan
Department of Pathology, University of Southern California, Los Angeles, CA, USA.
Wound Repair Regen. 2009 Sep-Oct;17(5):639-48. doi: 10.1111/j.1524-475X.2009.00535.x.
Differences in cellular competence offer an explanation for the differences in the healing capacity of tissues of various ages and conditions. The homeobox family of genes plays key roles in governing cellular competence. Of these, we hypothesize that Msx2 is a strong candidate regulator of competence in skin wound healing because it is expressed in the skin during fetal development in the stage of scarless healing, affects postnatal digit regeneration, and is reexpressed transiently during postnatal skin wound repair. To address whether Msx2 affects cellular competence in injury repair, 3 mm full-thickness excisional wounds were created on the back of C.Cg-Msx2(tm1Rilm)/Mmcd (Msx2 null) mice and the healing pattern was compared with that of the wild type mice. The results show that Msx2 null mice exhibited faster wound closure with accelerated reepithelialization plus earlier appearance of keratin markers for differentiation and an increased level of smooth muscle actin and tenascin in the granulation tissue. In vitro, keratinocytes of Msx2 null mice exhibit increased cell migration and the fibroblasts show stronger collagen gel contraction. Thus, our results suggest that Msx2 regulates the cellular competence of keratinocytes and fibroblasts in skin injury repair.
细胞能力的差异为不同年龄和状况的组织愈合能力差异提供了解释。基因的同源异型盒家族在调控细胞能力方面发挥着关键作用。其中，我们推测Msx2是皮肤伤口愈合中能力的一个强有力的候选调节因子，因为它在胎儿发育的无瘢痕愈合阶段在皮肤中表达，影响出生后指趾再生，并且在出生后皮肤伤口修复过程中短暂重新表达。为了探讨Msx2是否影响损伤修复中的细胞能力，在C.Cg-Msx2(tm1Rilm)/Mmcd（Msx2基因敲除）小鼠的背部制作3毫米全层切除伤口，并将愈合模式与野生型小鼠进行比较。结果显示，Msx2基因敲除小鼠表现出更快的伤口闭合，伴有上皮再形成加速以及分化角蛋白标志物更早出现，并且肉芽组织中平滑肌肌动蛋白和腱生蛋白水平增加。在体外，Msx2基因敲除小鼠的角质形成细胞表现出细胞迁移增加，而成纤维细胞显示出更强的胶原凝胶收缩。因此，我们的结果表明Msx2在皮肤损伤修复中调节角质形成细胞和成纤维细胞的细胞能力。
