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(American Journal of Pathology. 2000;157:1875-1882.)
© 2000 American Society for Investigative Pathology

Regular Articles

Facilitated Wound Healing by Activation of the Transglutaminase 1 Gene

Reiko Inada*, Masato Matsuki*, Keiko Yamada*, Yoichi Morishima*, Shen-Chun Shen*, Nobuo Kuramoto*, Hirokazu Yasuno*, Kenzo Takahashi{dagger}, Yoshiki Miyachi{dagger} and Kiyofumi Yamanishi*

From the Department of Dermatology,*
Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto; and the Department of Dermatology,{dagger}
Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, Japan

Transglutaminase 1 (TGase 1) is a Ca2+-dependent enzyme which catalyzes {epsilon}-({gamma}-glutamyl)lysine cross-linking of substrate proteins such as involucrin and loricrin to generate the cornified envelope at the cell periphery of the stratum corneum. We have shown that disruption of the TGase 1 gene in mice results in neonatal lethality, absence of the cornified envelope, and impaired skin barrier function. Based on the importance of TGase 1 in 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 that expression continued in the migrating epidermis until completion of re-epithelialization. The TGase 1 enzyme co-localized on the plasma membrane of migrating keratinocytes with involucrin, but not with loricrin, which suggests the premature assembly of the cornified envelope. Similar injuries to TGase 1 knockout mouse skins grafted on athymic nude mice showed substantial delays in wound healing concomitant with sustained K6{alpha} mRNA induction. From these results, we suggest that activation of the TGase 1gene is essential for facilitated repair of skin injury.




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