Regulation of MAPK activation, AP-1 transcription factor expression and keratinocyte differentiation in wounded fetal skin
Regulation of MAPK activation, AP-1 transcription factor expression and keratinocyte differentiation in wounded fetal skin
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DOI：
10.1111/j.0022-202x.2004.22319.x
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发表时间：
2004-03-01
影响因子：
6.5
通讯作者：
Rayner, TE
中科院分区：
文献类型：
--
作者：
Gangnuss, S;Cowin, AJ;Rayner, TE
在器官型培养中，胎儿上皮保留了伤口再上皮化的能力，而不依赖于皮下基质的存在。这种能力在妊娠晚期或胚胎第17天（E-17）之后丧失，因此胚胎第19天（E-19）伤口不能再上皮化。此外，E-17胎儿在子宫内产生的伤口以再生、无疤痕的方式愈合。为了研究调节胎儿皮肤再上皮化的分子事件，利用器官型胎儿培养，研究了E-17和E-19皮肤中伤口诱导的激活蛋白1 （AP-1）转录因子c-Fos和c-Jun的表达谱和组织定位。研究人员评估了丝裂原活化蛋白激酶（MAPK）信号在介导伤口诱导的转录因子表达和伤口再上皮化中的作用，并确定了损伤对角质细胞分化标志物表达的影响。我们的研究结果表明，AP-1转录因子在E-17和E-19皮肤损伤后立即被诱导表达，并且主要局限于表皮。c-fos和c-jun的诱导在E-17皮肤中是短暂的，mapk依赖性c-fos的表达是器官型培养中切除伤口再上皮化所必需的。在E-19皮肤中，AP-11的表达持续超过损伤后12小时，并且角化细胞分化标志物角蛋白10和loricrin明显上调。在E-17皮肤中，角蛋白10和loricrin的表达没有发生这种变化。这些发现表明，伤口诱导的AP-1转录因子通过MAPK表达和角质形成细胞的分化状态调节了胎儿皮肤的再上皮化。
Fetal epithelium retains the ability to re-epithelialize a wound in organotypic culture in a manner not dependent on the presence of underlying dermal substrata. This capacity is lost late in the third trimester of gestation or after embryonic day 17 (E-17) in the rat such that embryonic day 19 (E-19) wounds do not re-epithelialize. Moreover, wounds created in E-17 fetuses in utero heal in a regenerative, scar-free fashion. To investigate the molecular events regulating re-epithelialization in fetal skin, the wound-induced expression profile and tissue localization of activator protein 1 (AP-1) transcription factors c-Fos and c-Jun was characterised in E-17 and E-19 skin using organotypic fetal cultures. The involvement of mitogen-activated protein kinase (MAPK) signaling in mediating wound-induced transcription factor expression and wound re-epithelialization was assessed, with the effect of wounding on the expression of keratinocyte differentiation markers determined. Our results show that expression of AP-1 transcription factors was induced immediately by wounding and localized predominantly to the epidermis in E-17 and E-19 skin. c-fos and c-jun induction was transient in E-17 skin with MAPK-dependent c-fos expression necessary for the re-epithelialization of an excisional wound in organotypic culture. In E-19 skin, AP-11 expression persisted beyond 12 h post-wounding, and marked upregulation of the keratinocyte differentiation markers keratin 10 and loricrin was observed. No such changes in the expression of keratin 10 or loricrin occurred in E-17 skin. These findings indicate that re-epithelialization in fetal skin is regulated by wound-induced AP-1 transcription factor expression via MAPK and the differentiation status of keratinocytes.