Facilitated Wound Healing by Activation of the Transglutaminase 1 Gene

• Published in: The American journal of pathology Vol. 157; no. 6; pp. 1875 - 1882
• Main Authors: Inada, Reiko, Matsuki, Masato, Yamada, Keiko, Morishima, Yoichi, Shen, Shen-Chun, Kuramoto, Nobuo, Yasuno, Hirokazu, Takahashi, Kenzo, Miyachi, Yoshiki, Yamanishi, Kiyofumi
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.12.2000; ASIP; American Society for Investigative Pathology
• Subjects: Animals; Biological and medical sciences; Dermatology; Gene Expression Regulation; Keratins - genetics; Medical sciences; Mice; Mice, Inbred Strains; Mice, Knockout - genetics; Mice, Nude; Protein Precursors - genetics; Regular; RNA, Messenger - metabolism; Skin - injuries; Skin involvement in other diseases. Miscellaneous. General aspects; Skin Transplantation; Transglutaminases - genetics; Wound Healing - genetics; Wounds, Penetrating - physiopathology; Facilitation; Immunohistochemistry; Enzyme; Transferases; In situ; Rodentia; Activation; Hybridization; Aminoacyltransferases; Trauma; Wound; Pathology; Vertebrata; Experimental disease; Mammalia; Mouse; Animal; Skin; Protein-glutamine γ-glutamyltransferase; Molecular biology; Immunofluorescence; Cicatrization
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/S0002-9440(10)64826-2

Transglutaminase 1 (TGase 1) is a Ca 2+-dependent enzyme which catalyzes ε-(γ-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 6α 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 K6α mRNA induction. From these results, we suggest that activation of the TGase 1 gene is essential for facilitated repair of skin injury.