Abstract：
The Runt-related transcription factor (Runx) family has been suggested to play roles in stem cell regulation, tissue development, and oncogenesis in various tissues/organs. In this study, we investigated the possible functions of Runx1 and Runx3 in keratinocyte differentiation. Both Runx1 and Runx3 proteins were detected in primary cultures of mouse keratinocytes. Proteins were localized in the nuclei of undifferentiated keratinocytes but translocated to the cytoplasm of differentiated cells. The siRNA-mediated inhibition of Runx1 and Runx3 expression increased expression of keratin 1 and keratin 10, which are early differentiation markers of keratinocytes. In contrast, overexpression of Runx1 and Runx3 suppressed keratin 1 and keratin 10 expression. Endogenous Runx1 and Runx3 proteins were associated with the promoter sequences of keratin 1 and keratin 10 genes in undifferentiated but not differentiated keratinocytes. In mouse skin, the inhibition of Runx1 and Runx3 expression by keratinocyte-specific gene targeting increased the ratios of keratin 1- and keratin 10-positive cells in the basal layer of the epidermis. On the other hand, inhibition of Runx1 and Runx3 expression did not alter the proliferation capacity of cultured or epidermal keratinocytes. These results suggest that Runx1 and Runx3 likely function to directly inhibit differentiation-induced expression of keratin 1 and keratin 10 genes but are not involved in the regulation of keratinocyte proliferation.
摘要：
Runt相关转录因子（Runx）家族已被认为在干细胞调控中发挥作用。组织发育，和各种组织/器官的肿瘤发生。在这项研究中,我们研究了Runx1和Runx3在角质形成细胞分化中的可能功能。在小鼠角质形成细胞的原代培养物中检测到Runx1和Runx3蛋白。蛋白质位于未分化的角质形成细胞的细胞核中，但易位到分化细胞的细胞质中。siRNA介导的Runx1和Runx3表达的抑制增加了角蛋白1和角蛋白10的表达，这是角质形成细胞的早期分化标志物。相比之下,Runx1和Runx3的过表达抑制了角蛋白1和角蛋白10的表达。内源性Runx1和Runx3蛋白与未分化但未分化的角质形成细胞中角蛋白1和角蛋白10基因的启动子序列相关。在老鼠的皮肤上，通过角质形成细胞特异性基因靶向抑制Runx1和Runx3的表达增加了表皮基底层中角蛋白1-和角蛋白10-阳性细胞的比例。另一方面,抑制Runx1和Runx3表达不会改变培养或表皮角质形成细胞的增殖能力。这些结果表明，Runx1和Runx3可能具有直接抑制分化诱导的角蛋白1和角蛋白10基因表达的功能，但不参与角质形成细胞增殖的调节。
