Transglutaminase 2 mediates UVB‐induced matrix metalloproteinase‐1 expression by inhibiting nuclear p65 degradation in dermal fibroblasts

Matrix metalloproteinases (MMPs) play a key role in tissue remodeling by cleaving extracellular matrix (ECM) components. In the skin, UV-irradiation increases expression of MMPs that causes dysregulation of ECM homeostasis in dermis, leading to acceleration of skin aging. However, the mediator(s) that links UV-irradiation to the upregulation of MMPs have not been fully defined. Previously, we showed that UVB-irradiation activated transglutaminase 2 (TG2) in keratinocytes, eliciting an inflammatory response by activating NF-κB signaling. In this study, we reported the role of TG2 in mediating the UVB-induced expression of MMP-1. In human dermal fibroblasts, UVB-irradiation enhanced the expression and activity of TG2, which in turn promotes the expression of MMP-1. Analyses of MMP-1 promoter showed that activation of the NF-κB signaling pathway, rather than AP-1, was responsible for the TG2-mediated upregulation of MMP-1. Moreover, western blot analysis revealed that TG2 increased the activity of NF-κB by inhibiting degradation of p65 in the nucleus. Furthermore, ex vivo skin from TG2-knockout mice exhibited significantly reduced levels of MMP-1 compared to that from wild-type mice. These results indicate that TG2 functions as a mediator for the UVB-induced expression of MMP-1 in dermal fibroblasts, providing a new target for preventing skin photodamage.

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