Facilitated wound healing by activation of the Transglutaminase 1 gene

Transglutaminase 1 (TGase 1) is a Ca2+-dependent enzyme which catalyzes eps ilon-(gamma -glutamyl)lysine cross-linking of substrate proteins such as in volucrin and loricrin to generate the cornified envelope at the cell periph ery of the stratum corneum. We have shown that disruption of the TGase I ge ne in mice results in neonatal lethality, absence of the cornified. envelop e, and impaired skin barrier function. Based on the importance of TGase I i n epidermal morphogenesis, we have now assessed its role in wound healing. In neonatal mouse skin, TGase 1 mRNA as well as keratin 6 alpha was induced in the epidermis at the wound edges as early as 2 hours after injury and t hat expression continued in the migrating epidermis until completion of re- epithelialization. The TGase 1 enzyme co-localized on the plasma membrane o f migrating keratinocytes with involucrin, but not with loricrin, which sug gests the premature assembly of the cornified envelope. Similar injuries to TGase 1 knockout mouse skins grafted on athymic nude mice showed substanti al delays in wound healing concomitant with sustained K6 alpha mRNA inducti on. From these results, we suggest that activation of the TGase 1 gene is e ssential for facilitated repair of skin injury.