Contribution of transglutaminases and their substrate proteins to the formation of cornified cell envelope in oral mucosal epithelium.

Cornified envelope formation is crucial for the final differentiation of keratinized epithelium. However, the mechanisms of cornified envelope formation in the oral epithelium remain unclear. The aim of this study was to clarify the differences in the distribution and expression of cornified envelope related proteins and genes between keratinized and non-keratinized oral epithelia. We immunohistochemically investigated the distribution patterns of transglutaminase 1 (TG1), transglutaminase 3 (TG3), and their substrate proteins involucrin (IVL), loricrin (LOR), and small proline rich proteins (SPRs), in 19 keratinized and 14 non-keratinized oral epithelium samples. TG1 and TG3 mRNA levels were investigated in both types of epithelium by real time reverse transcription polymerase chain reaction (RT-PCR) using paraffin-embedded specimens. Data were analyzed to identify factors involved in cornified envelope formation. We demonstrate that 11 localization patterns show statistically significant differences between keratinized and non-keratinized oral epithelia. These factors clearly drove the separation of the two groups during cluster analysis. TG1 mRNA levels in keratinized oral epithelium were significantly higher than those in non-keratinized oral epithelium. In conclusion, the characteristic distribution of transglutaminases and their substrates and the mRNA levels of TG1 can regulate cornified envelope formation in keratinized oral epithelium, together with the contribution of TG3 first reported in this paper.