对FOXS1的TGF-β1依赖表达减弱了脂肪生成潜力,并增强了肌纤维细胞细胞表型
Alexander H Tavares1, Scott P Connelly1, Daryn Maksat1
1Department of Biochemistry and Cell Biology, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.
The Journal of biological chemistry
|August 7, 2025
概括
叉头盒 S1 (FOXS1) 通过增强转化生长因子-β1 (TGF-β1) 信号传递,促进白色脂肪组织纤维化,从而导致肌纤维细胞激活和阻断脂肪细胞发育.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 内分泌学 在内分泌学.
背景情况:
- 白脂肪组织 (WAT) 纤维化与肥胖和心脏代谢问题有关.
- 转化生长因子-β1 (TGF-β1) 驱动着脂肪细胞干细胞 (ASC) 中的肌纤维细胞激活.
- 在WAT纤维化和ASC激活中TGF-β1的确切作用需要进一步阐明.
研究的目的:
- 研究FOXS1在TGF-β1介导的信号传递在人类WAT ASC中的作用.
- 了解FOXS1在WAT纤维化背景下如何影响肌纤维细胞激活和脂肪生成.
主要方法:
- 确定FOXS1作为TGF-β1点在人类初级WAT ASC (hASC) 中.
- 在10T1/2纤维细胞中对FOXS1进行实验性操纵,以评估其对基因表达的影响.
- 在TGF-β1刺激和FOXS1调制后对肌纤维细胞和基因基因标记物的分析.
主要成果:
- 在hASC中,FOXS1是TGF-β1信号的直接转录标.
- 在纤维细胞中,FOXS1增强了TGF-β1诱导的益纤维细胞基因 (Acta2,Col1a1,Fn1,Il11) 的表达.
- FOXS1 抑制脂肪生成基因诱导 (Pparg,Stat5a,Fabp4,Adipoq) 并增强TGF-β1的抗脂肪生成作用.
- 失去FOXS1促进脂肪生成,并激活亲基的程序,即使在TGF-β1刺激下.
结论:
- 在脂肪组织中,FOXS1是TGF-β1在脂肪组织中的益纤维素作用的关键调解者.
- 福克斯1促进肌纤维细胞激活,同时抑制脂肪生成.
- 这些发现凸显了FOXS1在WAT纤维化中的关键作用,并表明其可能参与与肥胖有关的心脏代谢功能障碍.
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