糖尿病伤口角质细胞诱导巨细胞JMJD3-介导的Nlrp3通过IL-1R信号表达
Sonya J Wolf1, Christopher O Audu1, Jadie Y Moon1
1Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI.
Diabetes
|June 13, 2024
概括
糖尿病伤口角质细胞通过IL-1α发出信号,在巨细胞中增加JMJD3,激活NLRP3炎症酶并损害伤口愈合. 准这种途径可能会改善糖尿病伤口的修复.
科学领域:
- 伤口愈合 治愈 伤口愈合
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 巨细胞 (Mφ) 的可塑性对伤口修复至关重要,但在2型糖尿病中,Mφs仍然炎症,阻碍愈合.
- 在糖尿病伤口Mφs中观察到NLRP3炎症酶活性增加,但调节机制尚不清楚.
研究的目的:
- 阐明驱动糖尿病伤口愈合期间巨细胞NLRP3炎症酶激活的分子机制.
- 确定状细胞衍生信号和表观遗传修饰剂在调节Mφ NLRP3表达中的作用.
主要方法:
- 研究了糖尿病与非糖尿病伤口角质细胞中的IL-1α表达.
- 检查了Mφ NLRP3诱导中的IL-1受体介导信号.
- 评估了JMJD3表达及其在Nlrp3转录激活中通过H3K27me3.3的作用.
- 利用特定于骨髓细胞的JMJD3缺乏的小鼠 (Jmjd3f/flyz2Cre+) 在体内研究Mφ介导的Nlrp3表达.
主要成果:
- 糖尿病伤口角质细胞过度表达IL-1α,从而通过IL-1受体信号传递诱导Mφ Nlrp3的表达.
- 基因组脱甲基酶JMJD3在Mφs上调并由IL-1α诱导,导致Nlrp3的转录激活.
- 骨髓细胞中的JMJD3在糖尿病伤口愈合期间对Mφ介导的Nlrp3表达至关重要.
- 皮细胞衍生的IL-1α和IL-1R信号驱动NLRP3炎症酶在Mφs中的过度活跃,在非愈合的糖尿病伤口中.
结论:
- 在糖尿病伤口愈合过程中,状细胞衍生的IL-1α信号激活了Mφs中的NLRP3炎症酶.
- 作为一个关键的表观遗传调节剂,JMJD3在Mφs.中调解IL-1α诱导的Nlrp3表达.
- IL-1α/IL-1R/JMJD3轴代表了通过调节Mφ炎症酶活性来改善糖尿病伤口愈合的潜在治疗目标.
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