在脂肪细胞前体中由IL-4诱导的H19X编码的microRNAs调节增殖,以促进分化
Choijamts Munkhzul1,2, Ji-Min Lee1, Boseon Kim1,2
1Soonchunhyang Institute of Medi-bio Science, Soonchunhyang University, Cheonan, 31151, Korea.
Biology direct
|June 15, 2023
概括
介质素-4 (IL-4) 刺激白色脂肪组织前体细胞增殖和分化为热生成的色脂肪细胞. 由H19X位点编码的6个微RNA (miRNA) 通过与Wnt信号通路形成反循环来调节这个过程.
科学领域:
- 代谢和内分泌学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 脂肪组织对于能量恒温至关重要,并受到2型免疫的影响.
- 介质素-4 (IL-4) 促进脂肪细胞前体 (AP) 增殖和白色脂肪中的色脂肪细胞分化.
- 基于IL-4对APs影响的精确分子机制尚不完全理解.
研究的目的:
- 阐明IL-4调节脂肪细胞前体增殖和分化的分子机制.
- 确定关键的调节元件,包括参与IL-4介导脂肪生成的microRNA和信号通路.
主要方法:
- 刺激脂肪细胞前体 (APs) 的IL-4.
- 提升调节的微RNA (miRNA) 及其基因标的识别和表征.
- 对转录因子 (Klf4) 调节的分析.
- 使用LiCl处理调查Wnt信号通路的参与.
- 对miRNA对AP增殖和色脂肪细胞分化影响的评估.
主要成果:
- 六个H19X位点编码的miRNAs (miR-322,miR-503,miR-351,miR-542,miR-450a,miR-450b) 在AP中被IL-4上调,由Klf4.4调节.
- 这些miRNAs向参与Wnt信号传递的基因,包括Ccnd1和Fzd6,显示下调的mRNA表达.
- 在H19X小RNA和Wnt信号之间存在双负反循环,调节AP增殖和色脂肪细胞初始化.
- 异常的miRNA表达损害了色脂肪细胞分化.
结论:
- 编码H19X的miRNAs在调节脂肪细胞前体的增殖和分化方面发挥着至关重要的作用.
- 已识别的miRNA-Wnt信号反循环对于IL-4介导的色脂肪细胞发育至关重要.
- 这些发现为对热性脂肪细胞形成的分子控制提供了新的见解.
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