跨膜蛋白TMEM97和表观遗传阅读器BAHCC1构成了支持亲炎性细胞因子表达的轴
Jing Li1, Hongtao Shen1, Lian-Wang Guo2
1Division of Surgical Sciences, Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
Cellular signalling
|January 30, 2024
概括
我们发现了一种新的途径,其中TMEM97蛋白调节BAHCC1,然后通过NFκB通过视网膜色素上皮 (RPE) 细胞增加炎症. 这一发现揭示了视网膜退行性疾病背后的机制.
科学领域:
- 眼科医生 眼科 眼科
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 在视网膜退行性疾病中,视网膜色素表皮 (RPE) 产生的亲炎性细胞因子产生至关重要.
- 驱动RPE炎症的分子机制仍然不完全理解.
- 在此之前,TMEM97和BAHCC1在RPE炎症中的作用是未知的.
研究的目的:
- 研究TMEM97和BAHCC1在RPE细胞中调节促炎性细胞因子表达中的作用.
- 阐明在RPE炎症中连接TMEM97,BAHCC1和NFκB的分子级联.
主要方法:
- 对TMEM97-/- ARPE19细胞进行转录组分析.
- TMEM97功能损失和功能增益研究.
- 同免疫沉测定.
- 对NFκB路径进行分析.
- 使用RPE损伤视网膜退化的小鼠模型进行体内研究.
主要成果:
- TMEM97显著促进RPE细胞中促炎性细胞因子IL1β和CCL2,以及BAHCC1的表达.
- TMEM97和BAHCC1蛋白结合在一起,形成了一个新的调节轴.
- TMEM97调节NFκB激活,NFκB激活是炎症性细胞因子的关键转录因子.
- 沉默BAHCC1降低了NFκB和下游细胞因子的下调.
- 在视网膜退行模型中,Tmem97-/-小鼠表现出降低的IL1β,CCL2和质激活.
结论:
- TMEM97是RPE中促炎性细胞因子表达的新型决定因素.
- 一个以前未被描述的TMEM97 → BAHCC1 → NFκB级联调节RPE炎症.
- 针对这种途径可能为视网膜退行性疾病提供治疗策略.
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