Tgm2/Gh, Gbx1 and TGF-Beta Are Involved in Retinoic Acid-Induced Transdifferentiation from Epidermis to Mucosal Epithelium

The study demonstrated that retinoic acid (RA) induced the transdifferentiation of epidermal cells into mucosal epithelium with goblet cells in rat embryonic cultured skin. This process involved the upregulation of Gbx1, TG2/Gh, and TGF-beta proteins, with Gbx1 and TG2/Gh expressed in the epidermis and TGF-beta in the dermis. The transdifferentiation was partially inhibited by TGF-beta signal pathway inhibitors. Overexpression of both hTG2/Gh and mGbx1 in the epidermis led to changes in cell morphology, while RA directly transdifferentiated transient amplifying epidermal cells, not stem cells, into mucosal cells. The study concluded that coexpression of TG2/Gh and Gbx1 was necessary for esophagus-like mucosal transdifferentiation, and increased TGF-beta2 expression in the dermis was crucial for this process through epithelial-mesenchymal interaction.