Gasdermin C is induced by ultraviolet light and contributes to MMP-1 expression via activation of ERK and JNK pathways

Background: Ultraviolet (UV) radiation plays important roles in various skin diseases including premature aging and cancer. UV has been shown to regulate the expressions of many genes including matrix metalloproteinases (MMPs). Gasdermin C (GSDMC) belongs to Gasdermin family and is known to be expressed in the epithelial cells of many tissues including the skin. However, the functions of GSDMC remain poorly understood. Objective: We aimed to investigate the role of GSDMC in UV-induced MMP-1, MMP-3, and MMP-9 expressions in human skin keratinocytes. Methods: Primary human skin keratinocytes and an immortalized human skin keratinocyte cell line (HaCaT cells) were irradiated with UV. Knockdown and overexpression of GSDMC were performed to study the effect of GSDMC. The mRNA and protein levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting, respectively. Results: We found that GSDMC expression is increased by UV irradiation in human skin keratinocytes. Further studies showed that GSDMC expression is increased at relatively late time points after UV irradiation and that this GSDMC induction plays important roles in the expressions of MMP-1, but not of MMP-3 and MMP-9, and the activations of ERK and JNK induced by UV. In addition, we found that overexpression of GSDMC increases the MMP-1 expression and the activities of ERK and JNK and that GSDMC-induced MMP-1 expression is suppressed by inhibition of ERK or JNK activities. Conclusions: Our results suggest that GSDMC is increased by UV radiation and contributes to UV-induced MMP-1 expression through the activation of ERK and JNK pathways. (C) 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.