Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Department of Dermatology, Seoul National University Boramae Hospital, Seoul, Republic of Korea.
J Dermatol Sci. 2018 May;90(2):180-189. doi: 10.1016/j.jdermsci.2018.01.015. Epub 2018 Feb 1.
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.
We aimed to investigate the role of GSDMC in UV-induced MMP-1, MMP-3, and MMP-9 expressions in human skin keratinocytes.
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.
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.
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.
紫外线（UV）辐射在各种皮肤疾病中发挥着重要作用，包括皮肤过早衰老和皮肤癌。已证实，UV 可调节多种基因的表达，包括基质金属蛋白酶（MMPs）。Gasdermin C（GSDMC）属于 Gasdermin 家族，已知在包括皮肤在内的许多组织的上皮细胞中表达。然而，GSDMC 的功能仍知之甚少。
我们旨在研究 GSDMC 在 UV 诱导的人皮肤角质形成细胞中 MMP-1、MMP-3 和 MMP-9 表达中的作用。
用 UV 照射原代人皮肤角质形成细胞和永生化人皮肤角质形成细胞系（HaCaT 细胞）。进行 GSDMC 敲低和过表达以研究 GSDMC 的作用。通过实时定量聚合酶链反应（qRT-PCR）和 Western blot 分别分析 mRNA 和蛋白水平。
我们发现 GSDMC 在人皮肤角质形成细胞中经 UV 照射后表达增加。进一步的研究表明，GSDMC 的表达在 UV 照射后相对较晚的时间点增加，这种 GSDMC 诱导在 MMP-1 的表达中起重要作用，但在 MMP-3 和 MMP-9 的表达中不起作用，以及 UV 诱导的 ERK 和 JNK 的激活。此外，我们发现 GSDMC 的过表达增加 MMP-1 的表达和 ERK 和 JNK 的活性，并且 GSDMC 诱导的 MMP-1 表达被 ERK 或 JNK 活性的抑制所抑制。
我们的结果表明，GSDMC 是由 UV 辐射引起的，通过激活 ERK 和 JNK 途径促进 UV 诱导的 MMP-1 表达。
