Transglutaminase 3 Protects against Photodamage

Abstract

al. Study of clinical, biochemical and immunological factors determining stability of disease in patients with generalized vitiligo undergoing melanocyte transplantation. Br

Transglutaminase 3 Reduces the Severity of Psoriasis in Imiquimod-Treated Mouse Skin

“…We hypothesize that the absence of TG3 protein generates an impaired and more fragile epidermal barrier structure that facilitates percutaneous absorption and penetration of imiquimod through the skin. In this regard, our results are in agreement with Bognar [15] and with our recent study on the more profound sensitivity of TG3KO skin to UV radiation [16]. It is likely that higher levels of absorbed imiquimod in TG3KO mice intensify hyperproliferation and abnormal keratinocyte differentiation as a cutaneous response to the psoriasis-inducing drug.…”

“…Indeed, except for impaired hair development, TG3KO mice do not show evident morphological abnormalities and have an apparently normal cutaneous structure and skin barrier [12]. However, the epidermal barrier of TG3KO mice appeared slightly dysfunctional upon challenge, including increased susceptibility to hapten FITC uptake or increased sensitivity to UV radiation [15,16] TG2 is expressed in all epidermal layers, although its function in epidermal homeostasis is dispensable [21,22]. Dysregulation of pro-inflammatory TG2 activity elicits several inflammatory disorders [28][29][30]41].…”

“…In addition to its involvement in hair development, TG3 also contributes significantly to the proper formation of the cutaneous barrier because TG3KO mice skin displays increased permeability and susceptibility to the hapten fluorescein isothiocyanate (FITC) [15]. Moreover, our recent murine study demonstrated the importance of TG3 crosslinking activity in protecting skin from UV damage [16]. Impaired epidermal structure in TG3KO animals failed to shield against UVB radiation which thus penetrates deeper through the lower layers of epidermal keratinocytes, reaching the dermis and provoking high levels of DNA damage and apoptosis.A fourth enzyme, TG2, is widely diffused in various tissues and cell types.…”

Studies on differentiation‐dependent expression and activity of distinct transglutaminases by specific substrate peptides using three‐dimensional reconstituted epidermis

“…Recently, Frezza et al . revealed higher sensitivity of UV in TG3 KO mice, indicating TG3′s contribution to barrier formation. In their study, they also showed aberrant cross‐linking of substrates and a fragile CE in their epidermis.…”

Higher susceptibility to osmolality of the medaka (Oryzias latipes) mutants in orthologue genes of mammalian skin transglutaminases

“…Furthermore, knockout (KO) mice for each skin isozyme has been established except for TG5: TG1 KO mice show fragile skin formation leading to death after birth due to deprivation of water from body. In the case of TG3 KO mice, aberrant hair formation and susceptibility to UV were observed [4][5][6]. Thus, single and simultaneous knockdown of these skin enzymes leads to be lethal.…”