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Nelfb通过RNA聚合酶II介导的脂肪基因调节促进皮肤白色脂肪组织的形成

Samiksha Mahapatra¹, Julian Gomez¹, Uyanga Batzorig¹

¹Department of Dermatology, Department of Cellular and Molecular Medicine, Division of Epithelial Biology, University of California, San Diego, La Jolla, CA 92093-0869, USA.

Development (Cambridge, England)

|September 17, 2025

概括

转录暂停因子Nelfb对于皮肤白色脂肪组织 (dWAT) 的形成至关重要. 删除Nelfb会阻止脂肪细胞的分化并导致致死性,但恢复Pparg可以挽救这些效应.

科学领域:

细胞生物学细胞生物学
分子生物学分子生物学
皮肤病学皮肤病学

背景情况:

皮肤白色脂肪组织 (dWAT) 对于皮肤健康至关重要,支持再生,免疫力和伤口愈合.
dWAT的发育依赖于脂肪细胞前体的分化,这是由转录因子调节的过程.
转录暂停和延长在脂肪细胞分化中的作用仍然在很大程度上未被探索.

研究的目的:

研究转录暂停因子Nelfb在脂肪细胞分化和dWAT形成中的功能.
阐明Nelfb调节脂肪生成的分子机制.
确定是否针对Nelfb或其下游目标可以挽救脂肪生成缺陷.

主要方法:

在前脂肪细胞系中使用了具有Nelfb删除的小鼠模型.
分析了dWAT形成,脂肪基因表达和染色体结构.
使用逆转录病毒基因表达和药理学激动剂 (罗西格利塔) 来评估救生效应.

主要成果:

除Nelfb导致失败的dWAT和脂肪仓库形成,围产死亡率和减少基因表达.
发现Nelfb促进了开放的染色质,并稳定了RNA聚合酶II对关键脂肪基因的结合 (Pparg,Cebpa,Krox20,Stat3).
恢复Pparg表达或通过罗西格利塔激活它挽救了脂肪细胞分化和延长了Nelfb缺乏小鼠的寿命.

结论:

在促进dWAT形成所需的必需脂肪基因转录方面,Nelfb起着至关重要的作用.
转录暂停/延长是脂肪细胞分化中的关键调节机制.
针对Nelfb或其下游途径为涉及dWAT功能障碍的疾病提供了潜在的治疗策略.

关键词:

尼尔夫贝尔是自己的.在Ppargg中,Pparg是Pparg.脂肪细胞脂肪细胞增脂生殖是一种增脂的过程.这就是Cebpp的意义.皮肤上的白色脂肪.这就是Sox9x9的意义.转录延长转录延长转录性暂停转录性暂停没有信号发送.

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