Tumor necrosis factor-α downregulates the REIC/Dkk-3 tumor suppressor gene in normal human skin keratinocytes
Tumor necrosis factor-α downregulates the REIC/Dkk-3 tumor suppressor gene in normal human skin keratinocytes
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DOI：
10.3892/mmr.2018.8676
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发表时间：
2018-05-01
影响因子：
3.4
通讯作者：
Sakaguchi, Masakiyo
中科院分区：
文献类型：
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作者：
Kataoka, Ken;Maehara, Natsumi;Sakaguchi, Masakiyo
我们前期的研究发现REIC/Dkk-3在包括皮肤角质形成细胞在内的多种组织中均有表达。本研究的目的是确定调节dickkopf Wnt信号通路抑制剂3（REIC/Dkk-3）肿瘤抑制基因在正常人皮肤角质形成细胞（NHK）中表达的因素。几种生长因子和细胞因子，以前已经报道参与角质形成细胞的生长和分化的筛选作为潜在的调节剂。使用来自在有/没有各种因子（包括表皮生长因子、肿瘤坏死因子-α、转化生长因子-β、白细胞介素（IL）-1F9、IL-6、IL-8和Ca 2+）的情况下培养的NHK的蛋白质进行蛋白质印迹分析。结果表明，只有TNF-α下调NHK中的REIC/Dkk-3表达。随后，证实TNF-α降低小鼠皮肤组织和毛发培养模型中REIC/Dkk-3的表达水平。通过加入TNF-α特异性抗体，TNF-α介导的NHK中REIC/Dkk-3表达的下调被废除。总之，结果表明TNF-α下调REIC/Dkk-3在正常皮肤角质形成细胞中的表达。
Our previous studies revealed that REIC/Dkk-3 was expressed various tissues, including skin keratinocytes. The aim of the present study was to identify the factors that regulate the expression of the dickkopf Wnt signaling pathway inhibitor 3 (REIC/Dkk-3) tumor suppressor gene in normal human skin keratinocytes (NHKs). Several growth factors and cytokines that have previously been reported to be involved in the growth and differentiation of keratinocytes were screened as potential regulators. Western blot analysis was performed using protein from NHKs cultured with/without various factors including the epidermal growth factor, tumor necrosis factor-alpha, transforming growth factor-beta, interleukin (IL)-1F9, IL-6, IL-8 and Ca2+. The results indicated that only TNF-alpha downregulated REIC/Dkk-3 expression in NHKs. Subsequently, TNF-alpha was confirmed to reduce the expression levels of REIC/Dkk-3 in mouse skin tissue and hair culture models. TNF-alpha-mediated downregulation of REIC/Dkk-3 expression in NHKs was abrogated by the addition of a TNF-alpha-specific antibody. In conclusion, the results indicate that TNF-alpha downregulates REIC/Dkk-3 expression in normal skin keratinocytes.