DNase1L2 degrades nuclear DNA during corneocyte formation
DNase1L2 degrades nuclear DNA during corneocyte formation
复制标题
DOI：
10.1038/sj.jid.5700503
复制
发表时间：
2007-01-01
影响因子：
6.5
通讯作者：
Tschachler, Erwin
中科院分区：
文献类型：
--
作者：
Fischer, Heinz;Eckhart, Leopold;Tschachler, Erwin
脱氧核糖核酸酶 (DNase) 去除角质形成细胞 (KC) 核 DNA 是正常角质层 (SC) 形成的重要步骤。然而，迄今为止，DNA 降解酶的分子身份仍然难以捉摸。在这里，我们发现核酸内切酶 DNase1-like 2 (DNase1L2) 优先在表皮中表达，并且其表达与体外和体内 KC 的终末分化相关。在正常皮肤的活检中，DNase1L2 mRNA 经常出现在基底层 KC 中，并且 DNase1L2 蛋白在颗粒层中含量很高。与正常皮肤相比，DNase1L2 表达在角化不全的表皮（例如银屑病病变）中下调。在人体皮肤等效模型中，当 DNase1L2 基因表达被小干扰 RNA 抑制时，细胞核在 SC 的所有层中得以维持。综上所述，我们的数据表明 DNase1L2 在表皮 KC 终末分化过程中的 DNA 降解中发挥重要作用。
The removal of keratinocyte (KC) nuclear DNA by deoxyribonucleases (DNases) is an important step in the formation of normal stratum corneum (SC). However, the molecular identity of the DNA-degrading enzymes has so far remained elusive. Here we show that the endonuclease DNase1-like 2 (DNase1L2) is preferentially expressed in the epidermis and that its expression correlates with terminal differentiation of KC in vitro and in vivo. In biopsies of normal skin, DNase1L2 mRNA was regularly found in suprabasal KC and DNase1L2 protein was highly abundant in the stratum granulosum. In contrast to normal skin, DNase1L2 expression was downregulated in parakeratotic epidermis such as in psoriatic lesions. When DNase1L2 gene expression was knocked down by small interfering RNA in a human skin equivalent model, nuclei were maintained through all layers of the SC. Taken together, our data demonstrate that DNase1L2 plays an essential role in DNA degradation during terminal differentiation of epidermal KC.