Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 110‑744, Republic of Korea.
Department of Dermatology, Seoul National University College of Medicine, Seoul 110‑744, Republic of Korea.
Int J Mol Med. 2018 Nov;42(5):2859-2866. doi: 10.3892/ijmm.2018.3839. Epub 2018 Aug 24.
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.
Gasdermin (GSDM)-C 是 GSDM 基因家族的一员，在包括皮肤在内的各种组织类型的上皮细胞中表达。GSDMC 的表达受紫外线 (UV) 照射诱导，并有助于人类皮肤角质形成细胞中 UV 诱导的基质金属蛋白酶 1 的表达。然而，UV 照射如何诱导 GSDMC 的表达尚不清楚。本研究旨在探讨瞬时受体电位阳离子通道亚家族 V 成员 1 (TRPV1) 和钙/钙调磷酸酶信号通路在 UV 诱导的人皮肤角质形成细胞 GSDMC 表达中的作用。用 TRPV1 拮抗剂辣椒素和钌红处理可显著抑制 TRPV1 活性，从而抑制 UV 诱导的 GSDMC 表达，而 TRPV1 激动剂辣椒素直接激活 TRPV1 则增加 GSDMC 表达。结果表明，细胞外钙和钙调磷酸酶活性可能是 UV 诱导 HaCaT 细胞中 GSDMC 表达所必需的。此外，沉默或过表达活化 T 细胞核因子细胞质 1 (NFATc1)，均可分别降低或增加 UV 诱导的 GSDMC 表达。这些数据表明，TRPV1 可能在 UV 诱导的 GSDMC 表达中起重要作用，并且 UV 诱导的 GSDMC 表达可能通过钙/钙调磷酸酶/NFATc1 途径介导。
