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.

Nootkatol prevents ultraviolet radiation-induced photoaging via ORAI1 and TRPV1 inhibition in melanocytes and keratinocytes

“…During UV-induced wrinkle formation, increased [Ca 2+ ] i due to TRPV1 activation induces gasdermin-C gene expression. Gasdermin-C expression is mediated by the cytoplasmic 1 (NFATc1) pathway, wherein NFATc1 corresponds to the Ca 2+ /calcineurin/ nuclear factor of activated T cells [14]. Upregulated gasdermin-C expression increases the production of MMP-1, which dose-dependently degrades collagen and elastin fibers that maintain skin elasticity and block laxity [13,14].…”

“…Gasdermin-C expression is mediated by the cytoplasmic 1 (NFATc1) pathway, wherein NFATc1 corresponds to the Ca 2+ /calcineurin/ nuclear factor of activated T cells [14]. Upregulated gasdermin-C expression increases the production of MMP-1, which dose-dependently degrades collagen and elastin fibers that maintain skin elasticity and block laxity [13,14]. Moreover, it was reported that UV irradiation could also increase TRPV1 expression [22].…”

“…Research is therefore focused on inhibiting collagenase or elastase to block wrinkling, and on tyrosinase production to reduce pigmentation [11]. However, recent studies suggest that both MMP-1 production and melanogenesis involve intracellular Ca 2+ signaling, which is mediated by calcium ion channels [6,10,[12][13][14][15][16][17][18].…”

Emerging insights on the role of gasdermins in infection and inflammatory diseases

“…However, it was first shown to function as an oncogene in colorectal cancer 29 . GSDMC is expressed in the epithelium of the skin, and recently, it was shown that ultraviolet light (UV) can induce GSDMC expression in the skin via TRPV1/calcium/calcineurin/NFATc1 signalling 30 . GSDMC in its turn upregulates MMP‐1, an important mediator of tissue damage by UV irradiation, through activating ERK and JNK pathways 31 .…”

Association of GSDMC polymorphisms with lumbar disc herniation among Chinese Han population

“…Gasdermin C ( GSDMC ) is located on chromosome 8q24.21 region and is known to be expressed in epithelial cells of many tissues, including skin (Kusumaningrum, Lee, Yoon, Park, & Chung, 2018). Human GSDMC was upregulated in metastatic melanoma cells (Watabe et al, 2001).…”