Roll of skin antioxidant system in UV irradiation and epidermal morphogenesis/differentiation

皮肤抗氧化系统在紫外线照射和表皮形态发生/分化中的作用

• 批准号: 21591454
• 负责人: KAWACHI Yasuhiro
• 金额: $ 2.91万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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-21591454/
• 关键词: 酸化ストレス; Nrf2; ケラチノサイト; 紫外線; 皮膚老化

Ultraviolet (UV) radiation is one of the most important environmental factors involved in the pathogenesis of premature skin aging, termed photoaging. The harmful effects of UV in photoaging are associated with the generation of reactive oxygen species, and cellular antioxidants act to prevent the occurrence and reduce the severity of UV-induced photoaging. The transcription factor Nrf2 and its cytoplasmic anchor protein, Keap1, are central regulators of the cellular antioxidant response. Here, we investigated the role of the Nrf2. Keap1 pathway in photoaging using nrf2 gene-deficient (nrf2-/-) mice. Our results indicated that UVB-irradiated nrf2-/-mice showed accelerated photoaging, such as coarse wrinkle formation, loss of skin flexibility, epidermal thickening, and deposition of extracellular matrix in the upper dermis. In addition, nrf2-/-mice also showed an increase in cutaneous reactivity for the lipid peroxidation product 4-hydroxy-2-nonenal and a significant decrease in cutaneous glutathione level. These findings indicate that Nrf2 plays the important role in the protection against UVB-induced photoaging.

紫外线(UV)辐射是导致皮肤过早老化的重要环境因素之一，被称为光老化。紫外线在光老化过程中的有害作用与活性氧的产生有关，细胞抗氧化剂起到了预防和减轻紫外线诱导的光老化的作用。转录因子Nrf2及其胞质锚定蛋白Keap1是细胞抗氧化反应的中央调节因子。在这里，我们研究了NRF2的作用。Keap1通路在Nrf2基因缺陷(Nrf2-/-)小鼠光老化中的作用。我们的结果表明，UVB照射的NRF2-/-小鼠表现出加速的光老化，如粗糙的皱纹形成，皮肤失去弹性，表皮增厚，真皮上部细胞外基质沉积。此外，NRF2-/-小鼠皮肤对脂质过氧化产物4-羟基-2-壬烯醛的反应性增加，皮肤谷胱甘肽水平显著降低。这些结果表明，Nrf2在抗UVB诱导的光老化中起着重要作用。

项目成果

Essential role of Nrf2 in keratinocyte protection from UVA by quercetin

• DOI: 10.1016/j.bbrc.2009.06.136
• 发表时间: 2009-09-11
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Kimura, Shintarou;Warabi, Eiji;Ishii, Tetsuro
• 通讯作者: Ishii, Tetsuro

Overexpression of the Transcription Factor Yin-Yang-1 Suppresses Differentiation of HaCaT Cells in Three-Dimensional Cell Culture

• DOI: 10.1038/jid.2010.229
• 发表时间: 2011-01-01
• 期刊: JOURNAL OF INVESTIGATIVE DERMATOLOGY
• 影响因子: 6.5
• 作者: Taguchi, Shijima;Kawachi, Yasuhiro;Otsuka, Fujio
• 通讯作者: Otsuka, Fujio

The induction of tumor‐specific CD4+ T cells via major histocompatibility complex class II is required to gain optimal anti‐tumor immunity against B16 melanoma cell line in tumor immunotherapy using dendritic cells

• DOI: 10.1111/j.1600-0625.2008.00802.x
• 发表时间: 2009-04
• 期刊: Experimental Dermatology
• 影响因子: 3.6
• 作者: Y. Fujisawa;T. Nabekura;Tomohei Nakao;Yasuhiro Nakamura;Takenori Takahashi;Y. Kawachi;F. Otsuka;M. Onodera

Perforated ischiogluteal bursitis mimicking a gluteal decubitus ulcer in patients with spinal cord injury : report of 2 cases.

脊髓损伤患者出现类似臀肌褥疮溃疡的坐骨臀肌滑囊炎穿孔：2 例报告。

• 发表时间: 2010
• 期刊: Arch Dermatol. 146(8)
• 作者: Fujisawa Y;Ito M;Nakamura Y;Furuta J;Ishii Y;Kawachi Y;Otsuka F
• 通讯作者: Otsuka F

酸化ストレス応答因子Nrf2が皮膚の紫外線反応に果たす役割

氧化应激反应因子Nrf2在皮肤紫外线反应中的作用

• 发表时间: 2011
• 作者: Kawachi Y;Fujisawa Y;Furuta J;Nakamura Y;Ishii Y;Otsuka F;川内康弘
• 通讯作者: 川内康弘