增强剂介导的FOXO3表达通过激活自细胞促进MSC脂肪基分化
Pei Feng1, Peizhuo Pang2, Zehang Sun2
1Center for Biotherapy, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen 518003, PR China.
Biochimica et biophysica acta. Molecular basis of disease
|December 3, 2023
概括
增强剂调节FOXO3,通过自细胞激活促进介酶干细胞 (MSC) 脂肪分化. 这种FOXO3通路为骨质疏松症提供了潜在的治疗点.
科学领域:
- 干细胞生物学 干细胞生物学
- 分子差异化的分子机制.
- 骨质疏松症的发病因子
背景情况:
- 介质干细胞 (MSC) 分化成多种细胞类型,但它们的分化平衡在骨质疏松症中被破坏,有利于脂肪生成.
- 推动MSC差异化转变的确切机制仍然存在争议.
- 增强剂作为基因表达调节剂,与维持细胞身份有关,包括在分化过程中.
研究的目的:
- 在骨质疏松症的背景下,识别关键基因和参与介质干细胞 (MSC) 脂肪基分化的调控元素.
- 阐明增强剂在调节促进脂肪生成的身份基因表达中的作用.
- 研究增强剂调节基因影响MSC分化和自的机制.
主要方法:
- 集成的多omics数据 (RNA-seq,ChIP-seq,ATAC-seq) 来识别关键的身份基因.
- 使用西式涂抹来评估蛋白质表达 (FOXO3,基转录因子,自基质).
- 使用的油红O染色用于脂肪生成可视化和免疫组织化学/免疫光学用于蛋白质定位 (FOXO3,PPARγ,LC3B).
主要成果:
- 确定FOXO3作为一个关键的身份基因,在MSC脂肪生成过程中由增强剂调节.
- 证明FOXO3促进基转录因子 (PPARγ,CEBPα,CEBPβ),形成一个积极的反循环.
- 发现高FOXO3激活PI3K-AKT通路,增强自和调解MSC脂肪分化.
结论:
- 通过增强剂调节的FOXO3通过PI3K-AKT通路促进自,驱动MSC脂肪基分化.
- 增强剂调节的FOXO3通路是导致骨质疏松症的一个重要机制.
- 向增强剂调节的FOXO3为治疗骨质疏松症提供了一个有前途的治疗策略.
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