肌肉激素调节了人体多层中皮细胞中的纤维素表达和分泌
Tsuyoshi Sakai1, Young-Yeon Choo1, Shinya Mitsuhashi1
1Department of Cellular and Molecular Biology, University of Texas at Tyler Health Science Center, Tyler, Texas, United States.
American journal of physiology. Lung cellular and molecular physiology
|February 13, 2024
概括
肌肉蛋白 (Myocd) 通过Smad3激活肌介质细胞中的纤维素蛋白 (FN1) 基因表达,而血清反应因子 (SRF) 抑制它. 这一发现为预防膜纤维化提供了新的策略.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 纤维化研究 纤维化研究
背景情况:
- 膜纤维化涉及膜介质细胞 (PMCs) 切换到一个介质细胞表型 (MesoMT).
- 在MesoMT期间,PMCs产生细胞外基质 (ECM) 蛋白质,如纤维素 (FN1),有助于纤维化.
- 了解肌纤维细胞中的FN1调节对于准胸膜纤维化至关重要.
研究的目的:
- 为了研究纤维素菌素 (FN1) 基因表达在人类多介质细胞 (HPMC) 衍生的肌纤维细胞中的调节机制.
- 阐明肌肉激素 (Myocd) 和血清反应因子 (SRF) 在控制FN1表达中的作用.
主要方法:
- 在HPMC中对Myocd,Smad3和SRF进行基因沉默.
- 分析FN1促进体,包括Smad3和SRF结合元件.
- 同免疫沉和染色体免疫沉试验用于评估蛋白质相互作用和DNA结合.
主要成果:
- 肌肉细胞基因沉默显著降低了FN1的表达.
- Smad3基因沉默降低了FN1表达,而SRF基因沉默增加了它.
- Myocd通过Smad3激活FN1表达,SRF抑制它;SRF在Myocd结合方面与Smad3竞争.
结论:
- Myocd通过与Smad3转录因子的相互作用和激活来调节FN1基因激活.
- SRF作为FN1表达的抑制剂,可能通过与Smad3竞争Myocd结合.
- 这些发现揭示了在膜纤维化中FN1的新型调节途径,并表明了潜在的治疗点.
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