Sphk1通过HDAC4调节HMGB1并通过过敏性鼻炎中介于上皮质质炎
Wei Huang1, Xi Chen1, Zizhen Liu1
1Department of Otorhinolaryngology Head and Neck Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou 570311, Hainan Province, PR China.
这项研究揭示了HMGB1,Sphk1和HDAC4调节过敏性鼻炎 (AR) 中的 pyroptosis. 针对这些分子,特别是HDAC4,为AR提供了潜在的新疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子医学是分子医学.
背景情况:
- 过敏性鼻炎 (AR) 是一个普遍存在的全球健康问题.
- 热,一种编程细胞死亡的形式,在AR病变发生过程中起着重要作用.
- 了解AR中热的分子机制对于开发有效治疗方法至关重要.
研究的目的:
- 调查高流动性组盒子1 (HMGB1),斯芬哥辛激酶1 (Sphk1) 和希斯脱乙酶4 (HDAC4) 在人类鼻上皮细胞 (hNEC) 烧灭和AR中的作用.
- 在AR的背景下,阐明控制热的分子相互作用.
主要方法:
- 在体外AR细胞培养和体内AR小鼠模型的建立.
- 利用西方斑点,ELISA,组织学染色和流动细胞测量来进行基因和蛋白质表达分析.
- 使用染色体免疫沉降 (ChIP),共免疫沉降 (Co-IP) 和双露西法酶测定验证的分子相互作用.
主要成果:
- 在AR患者和模型中观察到Sphk1,HMGB1和炎症组分 (IL-18,IL-1β) 的升高水平.
- Sphk1倒置抑制的灰尘引发的hNEC火灭菌.
- 过度表达HDAC4抑制了HMGB1介导的热,HDAC4通过MEF2C调节HMGB1转录.
- Sphk1与CaMKII-δ相互作用,促进HDAC4的酸化并抑制其转位,HDAC4敲击逆转了效应.
结论:
- 在AR中,Sphk1,HMGB1和HDAC4是热的关键调节者.
- HDAC4在抑制HMGB1诱导的火灭菌中的作用及其对HMGB1的转录调节为潜在的治疗途径.
- 该Sphk1-CaMKII-δ-HDAC4通路提供了对AR分子机制和潜在药物点的见解.
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