克洛托/FGF23轴通过ERK/MAPK通路调节心肌细胞亡和细胞因子释放
Zheng Jia1, Qian Liu2, Ying Xie1
1Department of Cardiovascular Surgery, Yan'an Hospital Affiliated to Kunming Medical University, NO. 245 Renmin East Road, Panlong District, Kunming, 650051, Yunnan, China.
Cardiovascular toxicology
|September 13, 2023
概括
克洛托/FGF23轴对冠状动脉疾病 (CAD) 的进展至关重要. 克洛托通过抑制亡并通过ERK/MAPK通路促进增殖来保护心肌细胞,而FGF23则具有相反的效果.
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:
- 冠状动脉疾病 (CAD) 是全球死亡的主要原因.
- 克洛托/FGF23轴在CAD病变发生过程中的作用尚不清楚.
- 了解这一轴对于开发新型治疗策略至关重要.
研究的目的:
- 在CAD中阐明Klotho/FGF23轴的功能和潜在机制.
- 研究Klotho和FGF23对心肌细胞功能和存活的影响.
- 探索ERK/MAPK路径在调解这些效应中的参与.
主要方法:
- 在接受冠状动脉旁路移植 (CABG) 手术的CAD患者中分析Klotho和FGF23水平.
- 隔离和培养大鼠心肌细胞用于实验性操纵.
- 评估基因和蛋白质表达,细胞亡,细胞循环和增殖,使用QRT-PCR,免疫光,流细胞计和CCK-8测定等技术.
- 研究ERK/MAPK路径激活和下游信号分子.
主要成果:
- 在CAD患者中,Klotho水平在CABG后增加,而FGF23水平下降.
- 克洛托在心肌细胞中的过度表达抑制了亡,促进了增殖,并增加了促炎性标记物 (TGF-β1,NF-κB,AT-II,AP-1).
- 过度表达FGF23表现出相反的效果,并调节ERK/MAPK通路 (使用激动剂/抑制剂) 逆转了这些结果,涉及ERK/MAPK通路.
结论:
- 克洛托/FGF23轴在CAD进展中起着至关重要的作用.
- 克洛托通过调节ERK/MAPK通路,抑制细胞亡,促进细胞增殖,对心肌细胞产生保护作用.
- FGF23似乎对心肌细胞产生有害影响,其作用与Klotho相反,通过相同的途径进行介导.
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