普罗利尔内酶重塑了巨细胞的功能,作为一种新型的转录性核心调节剂,并抑制了纤维化
Shuang-Zhe Lin1, Wei-Jie Wu1,2, Yu-Qing Cheng1
1Department of Gastroenterology, Xin Hua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
Experimental & molecular medicine
|July 2, 2023
概括
普罗利尔内酶 (PREP) 作为巨细胞中的核转录核心调节剂,影响基因表达. 它的缺失加剧了肝纤维化,强调了PREP在这种疾病中的保护作用.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 病理学 病理学 病理学
背景情况:
- 巨细胞是关键的免疫细胞,调节宿主防御和组织平衡.
- 失调的巨细胞功能与各种疾病有关,包括肝纤维化.
- 转录调节对巨细胞功能至关重要,但其机制尚未完全理解.
研究的目的:
- 研究PREP在巨细胞转录调节中的作用.
- 在肝纤维化,特别是非酒精性脂肪肝炎 (NASH) 的情况下确定PREP的功能.
主要方法:
- 在骨髓衍生的巨细胞 (BMDMs) 中进行基因淘汰研究.
- 静止和极化BMDMs的转录组分析.
- 实验性非酒精性脂肪肝炎 (NASH) 模型.
- 染色体激烈标记 (CUT&Tag) 和共免疫沉试验.
- 对下游基因表达的分析,包括甲素B和D.
主要成果:
- 准备淘汰赛改变了静止和M1/M2极化BMDMs的转录组.
- 在实验NASH模型中没有PREP加重肝纤维化.
- PREP局部化到巨细胞核,并与转录因子PU.1.相互作用.
- PREP调节了与纤维化有关的基因,例如甲素B和D,这些基因在淘汰赛模型中过度表达.
结论:
- 在巨细胞核中,PREP 作为转录性核心调节剂起作用.
- 通过调节巨细胞功能,PREP在肝纤维化病原体中起着保护作用.
- 准PREP可能为肝纤维化提供治疗策略.
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