Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, 301-747, Republic of Korea.
Exp Cell Res. 2010 Nov 15;316(19):3263-71. doi: 10.1016/j.yexcr.2010.09.013. Epub 2010 Sep 25.
Paired-like homeodomain transcription factor 2 (PITX2) has been implicated as one of the genes responsible for Rieger syndrome. It has been also shown to play a central role during development. In this study, we investigated the functional role of PITX2 in keratinocyte differentiation. RT-PCR analysis showed that PITX2c isoform was predominantly expressed in a differentiation-dependent manner. Consistent with, immunohistochemical staining showed that PITX2 expression was increased in the upper layer of epidermis. When PITX2c was overexpressed in cultured keratinocytes by a recombinant adenovirus, the differentiation markers such as involucrin and loricrin were significantly increased at both mRNA and protein levels. In addition, PITX2c overexpression led to the decrease of cell growth, concomitantly with the upregulation of cell cycle-related genes p21. To investigate the effect of PITX2c in vivo, we microinjected PITX2c expression vector into zebrafish embryo. Interestingly, overexpression of PITX2c in zebrafish embryo led to the formation of horn-like structure and thickening of epidermis, together with the increase of keratin 8 (K8) expression. These results suggest that PITX2c has a role in proliferation and differentiation of epidermal keratinocytes.
配对同源盒转录因子 2（PITX2）已被认为是导致里格尔综合征的相关基因之一。它在发育过程中也发挥着核心作用。在本研究中，我们研究了 PITX2 在角质形成细胞分化中的功能作用。RT-PCR 分析表明，PITX2c 同工型主要以分化依赖的方式表达。免疫组织化学染色结果一致表明，PITX2 表达在上皮的上层增加。当通过重组腺病毒过表达培养的角质形成细胞中的 PITX2c 时，角蛋白标志物如 involucrin 和 loricrin 在 mRNA 和蛋白水平上均显著增加。此外，PITX2c 的过表达导致细胞生长减少，同时细胞周期相关基因 p21 的上调。为了研究 PITX2c 在体内的作用，我们将 PITX2c 表达载体微注射到斑马鱼胚胎中。有趣的是，斑马鱼胚胎中 PITX2c 的过表达导致角状结构的形成和表皮增厚，同时角蛋白 8（K8）的表达增加。这些结果表明 PITX2c 在表皮角质形成细胞的增殖和分化中起作用。
