线粒体乌比基酸酶的减少增加了由皮肤纤维细胞通过诱导ER应激激应激增加矩阵金属蛋白酶-1的分泌
Yushi Katsuyama1, Yuri Okano1, Hitoshi Masaki1,2
1CIEL CO., LTD, Sagamihara, Japan.
Photodermatology, photoimmunology & photomedicine
|June 20, 2023
概括
线粒体无基因酶 (MITOL) 降低激活了内质网膜 (ER) 的压力,导致通过NF-κB和IL-6信号在纤维细胞中增加了矩阵金属蛋白酶-1 (MMP-1) 的分泌.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 皮肤病学 皮肤病学
背景情况:
- 线粒体ubiquitin合酶 (MITOL) 蛋白质水平随着UVA暴露而降低.
- 击 (KD) 的米托尔增加纤维细胞分泌的矩阵金属蛋白酶-1 (MMP-1).
- 众所周知,米托尔可以抑制内质网膜 (ER) 压力.
研究的目的:
- 研究降低MITOL导致MMP-1过分分泌的机制.
- 澄清ER应激在皮肤纤维细胞中MITOL-KD诱导的MMP-1分泌中的作用.
主要方法:
- 准备的MITOL-敲除正常的人体皮肤纤维细胞 (NHDFs).
- 在NHDF中测量MMP-1蛋白水平.
- 通过量化拼接的X盒结合蛋白1 (sXBP1) mRNA和需要伊诺西的酶1α (IRE1α) 蛋白水平来评估ER压力.
主要成果:
- 米托尔-KD NHDFs 显示增强的MMP-1分泌通过介导的介素-6 (IL-6) 和核因子-卡帕B (NF-κB) 激活.
- 通过IL-6中和抗体和NF-κB抑制剂 (JSH23) 减少了MMP-1的分泌.
- 无论是MITOL-KD还是UVA辐射的NHDF都表现出增加的ER压力;图尼卡米辛也增加了MMP-1分泌.
结论:
- 在MITOL的下降会诱导MMP-1的过分分泌.
- 这个过程涉及到ER应激的激活,导致NF-κB和IL-6信号通路.
- 在MITOL水平与纤维细胞MMP-1分泌之间的关系中,ER压力起着至关重要的作用.
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