纤维细胞生长因子18通过AMPK/NOX4通路在小鼠中减弱纤维化
Jie Zhou1, Yanni Shou1, Qiaoyan Shi1
1School of Pharmaceutical Science, Wenzhou Medical University, 325035, Wenzhou, China.
概括
纤维细胞生长因子18 (FGF18) 通过减少氧化应激来缓解纤维化. 在慢性病模型中,FGF18激活AMPK/NOX4通路,抑制纤维化进展.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 管纤维化是慢性病 (CKD) 进展的关键驱动因素.
- 纤维细胞生长因子 (FGFs) 参与病理生理学,但FGF18的具体作用仍然难以捉摸.
- 了解FGF18的功能对于开发纤维化治疗新治疗策略至关重要.
研究的目的:
- 调查FGF18在纤维化病变发生过程中的作用.
- 阐明FGF18影响纤维化的潜在分子机制.
- 在纤维化的临床前模型中评估FGF18的治疗潜力.
主要方法:
- 在小鼠模型中使用叶酸 (FA) 诱导纤维化.
- 用转化生长因子β (TGF-β) 刺激人类近端管状 (HK-2) 细胞.
- 在脏中过度表达FGF18并评估纤维化标记物,氧化应激和信号通路 (AMPK,NOX4).
主要成果:
- 在FA诱导的纤维化和TGF-β刺激的HK-2细胞中,FGF18表达显著上调.
- 过度表达FGF18改善了FA诱导的纤维化和减少了氧化应激.
- FGF18通过FGFR3进行AMP激活蛋白激酶 (AMPK) 酸化,降低NOX4-ROS水平并抑制纤维化相关的蛋白质表达.
结论:
- FGF18表明对叶酸诱导的纤维化具有保护作用.
- 该机制涉及FGF18激活AMPK/NOX4通路,从而减少氧化应激和纤维化.
- 在慢性病中,FGF18代表了缓解纤维化的潜在治疗标.
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