Department of Physiological Chemistry II, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199–0195, Japan.
Biol Pharm Bull. 2011;34(8):1227-30. doi: 10.1248/bpb.34.1227.
We showed previously that transdifferentiation of skin epidermis to mucous epithelium can be induced by treatment with 20 µM retinol for 1 d followed by culture for 4 d without retinol in chick embryonic tarsometatarsal skin. In mouse epidermal cells, 3 µM retinoic acid (an active metabolite of retinol) inhibits epidermal keratinization in consistent with an increase in transglutaminase (TG)2/Gh, while its physiological role in the skin is still unresolved. TG1, TG3 and TG5 are also found in mammalian keratinocytes and play an important role in the formation of the stratum corneum in the skin by the introduction of cross-links into proteins. The most characteristic enzyme function of TG family is calcium-dependent transamidation activity (transamidase) that introduces inter or intramolecular ε-(γ-glutamyl)lysine cross-links into the protein. TG2/Gh is a multifunctional protein and ubiquitously expressed member of transglutaminase family that has been implicated in a variety of biological processes. By in situ hybridization analysis, we showed that TG2/Gh mRNA expression started to increase throughout the skin during the culture for 1 d with retinol, while it was weak in the control skin. On the other hand, an expression of TG3 mRNA was increased in the keratinized epidermis of control skin but was decreased by retinol. In situ transamidase activity of transglutaminase was weak in retinol-pretreated skin. Therefore, it was indicated that functions other than transamidase of TG2/Gh protein might be important in retinol-induced epidermal mucous transdifferentiation.
我们之前曾表明，通过用 20µM 视黄醇处理 1 天，然后在没有视黄醇的情况下培养 4 天，可将鸡胚胎跗跖皮的表皮向粘液上皮转化。在小鼠表皮细胞中，3µM 视黄酸（视黄醇的一种活性代谢物）抑制表皮角化，这与转谷氨酰胺酶 (TG)2/Gh 的增加一致，但其在皮肤中的生理作用仍未解决。TG1、TG3 和 TG5 也存在于哺乳动物角质形成细胞中，通过将交联引入蛋白质中，在皮肤中形成角质层发挥重要作用。TG 家族最具特征性的酶功能是钙依赖性转酰胺基活性（转酰胺酶），它将 ε-(γ-谷氨酰基)赖氨酸内或内分子交联引入蛋白质中。TG2/Gh 是一种多功能蛋白，是转谷氨酰胺酶家族中普遍表达的成员，它与多种生物过程有关。通过原位杂交分析，我们表明在含有视黄醇的培养基中培养 1 天时，TG2/Gh mRNA 表达开始在整个皮肤中增加，而在对照皮肤中则较弱。另一方面，在对照皮肤的角化表皮中 TG3 mRNA 的表达增加，但被视黄醇降低。转谷氨酰胺酶的原位转酰胺酶活性在视黄醇预处理的皮肤中较弱。因此，表明 TG2/Gh 蛋白的转酰胺酶以外的功能可能在视黄醇诱导的表皮粘液转化中很重要。
