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通过调节FOXO1的乙化,SIRT6的淘汰减轻了皮肤病中的角质细胞过度增殖和炎症

Chuantao Cheng¹, Yuan Wang¹, Jia Huo¹

¹Department of Dermatology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.

International immunopharmacology

|December 29, 2024

概括

在牛皮中,Sirtuin 6 (SIRT6) 的含量升高,导致质细胞的炎症和增殖. 抑制SIRT6促进FOXO1核转位,为牛皮治疗提供了潜在的治疗标.

科学领域:

皮肤病学皮肤病学
分子生物学分子生物学
生物化学生物化学

背景情况:

赛尔图因家族 (SIRT) 与各种疾病有关,但SIRT6在牛皮中的特定作用尚未完全理解.
牛皮是一种慢性炎症性皮肤疾病,具有复杂的潜在机制.

研究的目的:

为了研究SIRT6在牛皮病原发生中的作用.
探索SIRT6作为牛皮的潜在治疗点.

主要方法:

来自牛皮患者和健康捐赠者的RNA-seq数据的分析.
在体外研究中,使用使用M5.5治疗的HaCat细胞进行了实验.
在体内研究中,使用伊米基莫德诱导的牛皮的小鼠模型.
研究SIRT6倒置/抑制对炎症性细胞因子和细胞增殖的影响.
检查对分叉盒O 1 (FOXO1) 乙化和核转位的影响.

主要成果:

与非损伤或健康皮肤相比,SIRT6表达在病变性牛皮皮肤中显著上调.
在牛皮皮肤,小鼠模型和接受M5治疗的HaCat细胞中,SIRT6和Ki67的调节一直在上升.
抑制SIRT6的敲除/抑制抑制了M5诱导的炎症性细胞因子产生 (IL-1β,IL-6,TNF-α) 和角质细胞的增殖.
在小鼠模型中,SIRT6抑制降低了表皮厚度和Ki67表达.
SIRT6操纵影响了FOXO1乙化和核转位,影响了角质细胞的行为.

结论:

SIRT6在促进角质细胞过度增殖和牛皮炎炎症方面发挥着至关重要的作用.
抑制SIRT6通过增加其乙化来增强FOXO1核转位,从而抑制M5诱导的效应.
抑制SIRT6是牛皮的有希望的治疗策略.

关键词:

乙化乙化是一种这就是FOXO1的意义.过度扩散过度扩散氨酸细胞 (keratinocyte) 是一种细胞.牛皮是一种病.在SIRT6上.

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