Ultraviolet light-induced Gasdermin C expression is mediated via TRPV1/calcium/calcineurin/NFATc1 signaling

Abstract

Gasdermin (GSDM)-C is a member of the GSDM gene family and is expressed in the epithelial cells of various tissue types, including skin. GSDMC expression is induced by ultraviolet (UV) irradiation and contributes to UV-induced matrix metalloproteinase 1 expression in human skin keratinocytes. However, how UV irradiation induces GSDMC expression remains unclear. The present study aimed to investigate the role of transient receptor potential cation channel subfamily V member 1 (TRPV1) and a calcium/calcineurin-signaling pathway in UV-induced GSDMC expression in human skin keratinocytes. Suppression of TRPV1 activity by treatment with the TRPV1 antagonists capsazepine and ruthenium red significantly reduced UV-induced GSDMC expression, whereas direct activation of TRPV1 by capsaicin, a TRPV1 agonist, increased GSDMC expression. The results demonstrated that extracellular calcium and calcineurin activity may be necessary for UV-induced GSDMC expression in HaCaT cells. In addition, UV-induced GSDMC expression was either decreased or increased following knockdown or overexpression of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), respectively. These data suggested that TRPV1 may serve an important role in the induction of GSDMC expression by UV and that UV-induced GSDMC expression may be mediated via a calcium/calcineurin/NFATc1 pathway.