Analysis of molecular mechanisms and large-scale epidemiological study for tobacco smoke-related skin aging and diseases

烟草烟雾相关皮肤衰老和疾病的分子机制分析和大规模流行病学研究

• 批准号: 21390326
• 负责人: MORITA Akimichi
• 金额: $ 11.56万
• 依托单位: Nagoya City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390326/
• 关键词: 環境因子; 喫煙; 紫外線; 皮膚老化; 乾癬; 掌蹠膿疱症

The JAGE study(study of the extrinsic skin aging of JApanese and GErman women) is a cross-sectional study to investigate the possible reasons for differences in the manifestation of extrinsic skin aging between Asian and Caucasian European women. Japanese women had significantly more pigment spots on their cheeks than German women. In contrast, Japanese women had fewer wrinkles. The pigmentation was related to smoking and air pollution. Tobacco smoking increases the risk of psoriasis, but the mechanisms are not clear. We evaluated the percentage of circulating Th17.More smokers than nonsmokers had high Th17 levels. Tobacco smoke extract induced Th17 generation from central memory T cells in vitro. Epidemiologic studies suggest a link between smoking and extrinsic skin aging, and we previously reported that matrix metalloproteinases(MMPs) mediate connective tissue damage in skin exposed to tobacco smoke extracts. Tobacco smoke contains more than 3800 constituents, including numerous wat … More er insoluble polycyclic aromatic hydrocarbons that trigger the aryl hydrocarbon receptor(AhR ; also called the dioxin receptor) signaling pathway. To analyze the molecular mechanisms involved in tobacco smoke. induced skin aging, we exposed primary human fibroblasts and keratinocytes to tobacco smoke extracts. Hexane-and water-soluble tobacco extracts significantly induced MMP-1 mRNA in both human cultured fibroblasts and keratinocytes in a dose-dependent manner. To clarify the involvement of the AhR pathway, we used stable knockdown cell lines for AhR in HaCaT cells. AhR knockdown abolished the increase in transcription of the AhR-dependent gene CYP1A1/CYP1B1 and MMP-1 upon treatment with either tobacco smoke extract. Likewise, treating fibroblasts with AhR pathway inhibitors blocked the induction of CYP1B1 and MMP-1.These findings suggest that the tobacco smoke extracts induced MMP-1 expression in human fibroblasts and keratinocytes via activation of the AhR pathway. Thus, the AhR pathway may be pathogenetically involved in extrinsic skin aging. Less

JAGE研究（日本和德国女性外在皮肤老化研究）是一项横断面研究，旨在调查亚洲和高加索欧洲女性外在皮肤老化表现差异的可能原因。日本女性脸颊上的色素斑明显多于德国女性。相比之下，日本女性的皱纹较少。色素沉着与吸烟和空气污染有关。吸烟会增加牛皮癣的风险，但其机制尚不清楚。我们评估了循环中Th 17的百分比，吸烟者比不吸烟者有更多的Th 17水平。烟草烟雾提取物体外诱导中枢记忆T细胞产生Th 17。流行病学研究表明，吸烟和外在的皮肤老化之间的联系，我们以前报道，基质金属蛋白酶（MMPs）介导的结缔组织损伤皮肤暴露于烟草烟雾提取物。烟草烟雾含有超过3800种成分，其中包括大量的水。 ...更多信息 不溶性多环芳烃，触发芳烃受体（AhR ;也称为二恶英受体）信号通路。分析烟草烟雾的分子机制。诱导皮肤老化，我们暴露原代人成纤维细胞和角质形成细胞的烟草烟雾提取物。己烷和水溶性烟草提取物显着诱导MMP-1 mRNA在人培养的成纤维细胞和角质形成细胞中的剂量依赖性的方式。为了阐明AhR通路的参与，我们在HaCaT细胞中使用AhR的稳定敲低细胞系。AhR敲除废除了AhR依赖性基因CYP 1A 1/CYP 1B 1和MMP-1的转录增加后，治疗与烟草烟雾提取物。同样地，用AhR通路抑制剂处理成纤维细胞可阻断CYP 1B 1和MMP-1的诱导。这些结果表明，烟草烟雾提取物通过激活AhR通路诱导人成纤维细胞和角质形成细胞MMP-1的表达。因此，AhR途径可能在致病性参与外在皮肤老化。少

项目成果

Dermatological Phototherapy and Photodiagnostic methods(2nd ed),(J.Krutmann, H.Honigsmann, P.R.Bergstresser, C.A.Elmets, eds.)

皮肤病光疗和光诊断方法（第二版）（J.Krutmann、H.Honigsmann、P.R.Bergstresser、C.A.Elmets 编辑）

• 发表时间: 2009
• 作者: Jean Krutmann;Akimichi Morita;Craig A.Elmets
• 通讯作者: Craig A.Elmets

Tobacco smoke is related to Th17 generation with clinical implications for psoriasis patients

• DOI: 10.1111/j.1600-0625.2010.01224.x
• 发表时间: 2011-04-01
• 期刊: EXPERIMENTAL DERMATOLOGY
• 影响因子: 3.6
• 作者: Torii, Kan;Saito, Chiyo;Morita, Akimichi
• 通讯作者: Morita, Akimichi

Recent Advances in Skin aging

皮肤老化的最新进展

• 发表时间: 2011
• 作者: Kawamura M;Itoh H;Yura S;Mogami H;Fujii T;Kanayama N;Konishi I;Akimichi Morita
• 通讯作者: Akimichi Morita

The development of a filter to enhance the efficacy and safety of excimer light (308nm) therapy

开发滤光片以增强准分子光（308nm）治疗的功效和安全性

• 发表时间: 2009
• 期刊: Photodermatol Photoimmunol Photomed. 25
• 作者: Akimichi Morita;Keiko Kobayashi
• 通讯作者: Keiko Kobayashi

Ultraviolet A and UVB Phototherapy, in Therapy of skin diseases

紫外线A和UVB光疗，用于治疗皮肤病

• 发表时间: 2010
• 作者: Shiho Sakuma;Eiko Otake;Akira Maeda;Kan Torii;Shigenobu Yano;Hiromi Ooi;Akimichi Morita;Akimichi Morita
• 通讯作者: Akimichi Morita