纤维细胞生长因子21 通过p38 促进血管光滑肌肉细胞收缩极化 线素激活蛋白激酶促进血清反应因子酸化
Mengmeng Zhu1, Wenya Zhu1, Jianyuan Pan2
1Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, Anhui Provincial International Science and Technology Cooperation Base for Major Metabolic Diseases and Nutritional Interventions, School of Food and Biological Engineering, Hefei University of Technology, Hefei, China.
Research (Washington, D.C.)
|August 6, 2025
概括
纤维细胞生长因子21 (FGF21) 缺乏通过促进光滑肌肉细胞的变化,使血管疾病恶化. 然而,FGF21疗法在治疗与异常光滑肌肉细胞功能相关的血管疾病方面表现有前途.
科学领域:
- 心血管生物学 心血管生物学
- 内分泌学 在内分泌学.
- 分子医学是分子医学.
背景情况:
- 血管光滑肌细胞 (VSMC) 表型异常是血管疾病进展的关键驱动因素.
- 纤维细胞生长因子21 (FGF21) 是一种具有已知的代谢作用的激素,但它对VSMC的影响需要阐明.
研究的目的:
- 研究FGF21在调节VSMC表型中的作用及其作为血管疾病治疗点的潜力.
主要方法:
- 在人类和小鼠血管组织和血中分析FGF21表达.
- 使用FGF21缺乏和野生类型小鼠的体内研究,包括结合诱导的neointima形成模型.
- 对人类大动脉光滑肌细胞 (HASMC) 的体外研究,以评估FGF21对表型和信号通路的影响.
- 研究涉及p38 MAPK,SRF和肌肉细胞的分子机制.
主要成果:
- 人类和小鼠的新型心脏中FGF21水平降低,在动脉样硬化冠状动脉疾病和静脉复缩患者中降低.
- 在小鼠中,FGF21缺乏症加剧了内增生症,并减少了收缩性VSMCs.
- 重组FGF21的使用减弱了neointima形成,这种影响取决于VSMC特有的β-klotho.
- 在体外,FGF21通过p38 MAPK和SRF-肌肉激素复合体激活促进了VSMC收缩表型.
- FGF21模拟的efruxifermin和p38 MAPK激活抑制了新密度的形成.
结论:
- 通过维护VSMC收缩表型,FGF21对血管疾病起着保护作用.
- 特别是通过p38 MAPK和SRF-myocardin的FGF21信号,直接影响VSMC的行为.
- 调节FGF21或其下游途径代表了涉及VSMC表型转变的血管疾病的潜在治疗策略.
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