Transdifferentiation of epidermis to mucous epithelium by retinol accompanies increase in transglutaminase 2/Gh and decrease in transglutaminase 3.

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.