Sur Inderpreet, Rozell Björn, Jaks Viljar, Bergström Asa, Toftgård Rune
Department of Bioscience and Nutrition, Clinical Research Center, and Department of Laboratory Medicine Division of Pathology, Karolinska Institutet, Novum, SE-141 57 Huddinge, Sweden.
J Cell Sci. 2006 Sep 1;119(Pt 17):3593-601. doi: 10.1242/jcs.03070. Epub 2006 Aug 15.
Krüppel-like factor5 (Klf5) is a zinc-finger transcription factor normally expressed in the skin. Here, we show that overexpression of Klf5 in the basal layer of the epidermis during embryogenesis affects epidermal development and disrupts epithelial-mesenchymal interactions necessary for skin adnexae formation as well as craniofacial morphogenesis. The transgenic mice exhibited exencephaly, craniofacial defects, persistent abdominal herniation and ectodermal dysplasia. Moreover, the epidermis was hypoplastic and underwent abnormal differentiation with expression of keratin8, a marker for single-layered epithelia, in the stratified epidermis. Correspondingly, we observed a downregulation of DeltaNp63 expression in the skin. Overexpression of Klf5 in adult mice led to hyperkeratosis, follicle occlusion and epidermal erosions. Further, we observed decrease and even loss of the stem cell population of bulge keratinocytes, as characterized by the expression pattern of alpha6 integrin and CD34 markers. Our data suggest a new role of Klf5 as a modulator of p63 expression and the differentiation program of epidermal cells relevant for regenerative potential of the epidermis and epithelial-mesenchymal interactions.
Krüppel样因子5（Klf5）是一种通常在皮肤中表达的锌指转录因子。在此，我们表明在胚胎发育过程中表皮基底层中Klf5的过表达会影响表皮发育，并破坏皮肤附属器形成以及颅面形态发生所必需的上皮-间充质相互作用。转基因小鼠表现出脑膨出、颅面缺陷、持续性腹疝和外胚层发育异常。此外，表皮发育不全，并在分层表皮中出现异常分化，伴有单层上皮标志物角蛋白8的表达。相应地，我们观察到皮肤中DeltaNp63表达下调。成年小鼠中Klf5的过表达导致角化过度、毛囊闭塞和表皮糜烂。此外，我们观察到以α6整合素和CD34标志物的表达模式为特征的隆突角质形成干细胞群体减少甚至丧失。我们的数据表明Klf5作为p63表达的调节剂以及与表皮再生潜能和上皮-间充质相互作用相关的表皮细胞分化程序具有新的作用。
