白细胞介素-1α通过细胞内ERK/JNK/c-Jun/c-Fos/AP-1信号轴介导,刺激成人真皮成纤维细胞中皱纹诱导弹性蛋白酶神经纤溶酶的表达。

Mariko Takada, Uma Chandula Pinnawala, Shinichi Hirano, Genji Imokawa
{"title":"白细胞介素-1α通过细胞内ERK/JNK/c-Jun/c-Fos/AP-1信号轴介导,刺激成人真皮成纤维细胞中皱纹诱导弹性蛋白酶神经纤溶酶的表达。","authors":"Mariko Takada, Uma Chandula Pinnawala, Shinichi Hirano, Genji Imokawa","doi":"10.1111/1346-8138.17520","DOIUrl":null,"url":null,"abstract":"<p><p>Neprilysin is a skin wrinkle-inducing membrane bound elastase that is expressed abundantly in UV-exposed and in aged dermal fibroblasts. The overexpression of neprilysin is closely associated with enhanced epithelial-mesenchymal cytokine interactions mainly via interleukin (IL)-1α, which has the distinct potential to stimulate the expression of neprilysin by human dermal fibroblasts (HDFs). The over-expression of neprilysin also accelerates the formation of wrinkles, accompanied by disruptions of the three-dimensional architecture of dermal elastic fibers that are responsible for the loss of skin elasticity. Because the signaling pathway(s) that lead to the IL-1α-stimulated expression of neprilysin in HDFs remain unclear, we characterized the signaling pathway involved, including their related transcription factors, in IL-1α-treated HDFs. Since qRT-PCR analysis revealed that the mRNA expression level of neprilysin is stimulated to a stronger extent in adult HDFs (aHDFs) by IL-1α than in neonatal HDFs, we used aHDFs for the signaling analysis. Western blotting analysis of the phosphorylation of signaling factors revealed that IL-1α significantly stimulated the phosphorylation of ERK1/2, RSK, JNK, p38, MSK1, NFkB, c-Jun, ATF-2, CREB, and STAT3. Analysis using various signaling inhibitors demonstrated that inhibiting ERK and JNK but not p38, MSK1, NFkB, or STAT3 significantly abrogated the IL-1α stimulated expression of neprilysin at the mRNA, protein, and enzyme activity levels. Furthermore, silencing c-Fos significantly down-regulated the IL-1α-increased expression of neprilysin at the protein and enzyme activity levels. These findings strongly suggest that the IL-1α-stimulated expression of neprilysin in aHDFs is mediated via the intracellular signaling axis of ERK/JNK/c-Jun/c-Fos/AP-1.</p>","PeriodicalId":94236,"journal":{"name":"The Journal of dermatology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The interleukin-1α stimulated expression of the wrinkle-inducing elastase neprilysin in adult human dermal fibroblasts is mediated via the intracellular signaling axis of ERK/JNK/c-Jun/c-Fos/AP-1.\",\"authors\":\"Mariko Takada, Uma Chandula Pinnawala, Shinichi Hirano, Genji Imokawa\",\"doi\":\"10.1111/1346-8138.17520\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Neprilysin is a skin wrinkle-inducing membrane bound elastase that is expressed abundantly in UV-exposed and in aged dermal fibroblasts. The overexpression of neprilysin is closely associated with enhanced epithelial-mesenchymal cytokine interactions mainly via interleukin (IL)-1α, which has the distinct potential to stimulate the expression of neprilysin by human dermal fibroblasts (HDFs). The over-expression of neprilysin also accelerates the formation of wrinkles, accompanied by disruptions of the three-dimensional architecture of dermal elastic fibers that are responsible for the loss of skin elasticity. Because the signaling pathway(s) that lead to the IL-1α-stimulated expression of neprilysin in HDFs remain unclear, we characterized the signaling pathway involved, including their related transcription factors, in IL-1α-treated HDFs. Since qRT-PCR analysis revealed that the mRNA expression level of neprilysin is stimulated to a stronger extent in adult HDFs (aHDFs) by IL-1α than in neonatal HDFs, we used aHDFs for the signaling analysis. Western blotting analysis of the phosphorylation of signaling factors revealed that IL-1α significantly stimulated the phosphorylation of ERK1/2, RSK, JNK, p38, MSK1, NFkB, c-Jun, ATF-2, CREB, and STAT3. Analysis using various signaling inhibitors demonstrated that inhibiting ERK and JNK but not p38, MSK1, NFkB, or STAT3 significantly abrogated the IL-1α stimulated expression of neprilysin at the mRNA, protein, and enzyme activity levels. Furthermore, silencing c-Fos significantly down-regulated the IL-1α-increased expression of neprilysin at the protein and enzyme activity levels. These findings strongly suggest that the IL-1α-stimulated expression of neprilysin in aHDFs is mediated via the intracellular signaling axis of ERK/JNK/c-Jun/c-Fos/AP-1.</p>\",\"PeriodicalId\":94236,\"journal\":{\"name\":\"The Journal of dermatology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-10-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The Journal of dermatology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1111/1346-8138.17520\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Journal of dermatology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1111/1346-8138.17520","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

肾蛋白酶是一种皮肤皱纹诱导膜结合弹性蛋白酶,在紫外线暴露和老化的真皮成纤维细胞中大量表达。neprilysin的过度表达与上皮-间质细胞因子相互作用的增强密切相关,主要是通过白细胞介素(IL)-1α。肾蛋白酶的过度表达也会加速皱纹的形成,同时真皮弹力纤维的三维结构也会受到破坏,从而导致皮肤失去弹性。由于导致IL-1α刺激HDFs中肾素表达的信号通路仍不清楚,我们对IL-1α处理的HDFs中涉及的信号通路(包括其相关转录因子)进行了表征。qRT-PCR分析显示,IL-1α对成人HDFs(aHDFs)中肾蛋白酶mRNA表达水平的刺激程度比新生HDFs更强,因此我们使用aHDFs进行信号传导分析。信号因子磷酸化的 Western 印迹分析显示,IL-1α 能显著刺激 ERK1/2、RSK、JNK、p38、MSK1、NFkB、c-Jun、ATF-2、CREB 和 STAT3 的磷酸化。使用各种信号抑制剂进行的分析表明,抑制 ERK 和 JNK,而不是 p38、MSK1、NFkB 或 STAT3,可在 mRNA、蛋白质和酶活性水平上显著降低 IL-1α 刺激的肾蛋白表达。此外,沉默 c-Fos 能在蛋白和酶活性水平上显著下调 IL-1α 增加的肾小球酶的表达。这些发现有力地表明,IL-1α刺激的肾上皮素在aHDFs中的表达是通过细胞内ERK/JNK/c-Jun/c-Fos/AP-1信号轴介导的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The interleukin-1α stimulated expression of the wrinkle-inducing elastase neprilysin in adult human dermal fibroblasts is mediated via the intracellular signaling axis of ERK/JNK/c-Jun/c-Fos/AP-1.

Neprilysin is a skin wrinkle-inducing membrane bound elastase that is expressed abundantly in UV-exposed and in aged dermal fibroblasts. The overexpression of neprilysin is closely associated with enhanced epithelial-mesenchymal cytokine interactions mainly via interleukin (IL)-1α, which has the distinct potential to stimulate the expression of neprilysin by human dermal fibroblasts (HDFs). The over-expression of neprilysin also accelerates the formation of wrinkles, accompanied by disruptions of the three-dimensional architecture of dermal elastic fibers that are responsible for the loss of skin elasticity. Because the signaling pathway(s) that lead to the IL-1α-stimulated expression of neprilysin in HDFs remain unclear, we characterized the signaling pathway involved, including their related transcription factors, in IL-1α-treated HDFs. Since qRT-PCR analysis revealed that the mRNA expression level of neprilysin is stimulated to a stronger extent in adult HDFs (aHDFs) by IL-1α than in neonatal HDFs, we used aHDFs for the signaling analysis. Western blotting analysis of the phosphorylation of signaling factors revealed that IL-1α significantly stimulated the phosphorylation of ERK1/2, RSK, JNK, p38, MSK1, NFkB, c-Jun, ATF-2, CREB, and STAT3. Analysis using various signaling inhibitors demonstrated that inhibiting ERK and JNK but not p38, MSK1, NFkB, or STAT3 significantly abrogated the IL-1α stimulated expression of neprilysin at the mRNA, protein, and enzyme activity levels. Furthermore, silencing c-Fos significantly down-regulated the IL-1α-increased expression of neprilysin at the protein and enzyme activity levels. These findings strongly suggest that the IL-1α-stimulated expression of neprilysin in aHDFs is mediated via the intracellular signaling axis of ERK/JNK/c-Jun/c-Fos/AP-1.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信