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

Abstract

Background: Ultraviolet (UV) irradiation contributes various skin diseases including photoaging, cancer and inflammation. UV is known to regulate the expression of a wide variety of genes including matrix metalloproteinases (MMPs). Gasdermin C (GSDMC) belongs to Gasdermin family and is known to be expressed in epithelial cells and metastatic melanoma cells. However, the functions of GSDMC in the skin have not been reported yet. Objective: In this study, we investigated the regulation of GSDMC expression by UV and the role of GSDMC in the expressions of various MMPs induced by UV in human skin tissues and human skin keratinocytes. Methods: Human skin, normal human epidermal keratinocytes (NHEK) and an immortalized human keratinocyte cell line (HaCaT cell) were irradiated with UV. Knockdown or overexpression of GSDMC was performed to study the effect of GSDMC. mRNA and protein levels of many targets were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. GSDMC expression in human skin was also analyzed by immunohistochemical staining. Results: UV irradiation increased GSDMC expression at the mRNA and protein levels in human skin, NHEK and HaCaT cells. Knockdown of GSDMC reduced the MMP-1 expression and the ERK and JNK activities induced by UV. Furthermore, overexpression of GSDMC increased the MMP-1 expression and the activities of ERK and JNK. Conclusion: Our results show that GSDMC is increased by UV irradiation, which contributes to the increase in MMP-1 expression via activation of ERK and JNK pathways. Therefore, we suggest that GSDMC plays an important role in UV-induced MMP-1 expression.