克鲁佩尔之类因子5调节核因子 - - 红色素-2-相关因子2/血氧酶1信号通路 - - 调节腹腔大动脉动脉瘤中的血管光滑肌细胞亡
Guangwei Yang1, Cong Yu1, Chao Weng1
1General Surgery, Cancer Center, Department of Vascular Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, China.
Clinical and experimental pharmacology & physiology
|February 8, 2026
概括
克鲁佩尔样因子5 (KLF5) 通过抑制铁和血管化来保护腹腔大动脉动脉瘤 (AAA). 这种保护作用是通过核因子红色素-2-相关因子2/血红素酶1 (NRF2/HO-1) 途径进行的.
科学领域:
- 血管生物学 血管生物学
- 疾病的细胞机制.
- 分子信号通路 分子信号通路
背景情况:
- 腹腔大动脉动脉瘤 (AAA) 涉及大动脉扩张和破裂,原因不明.
- 血管光滑肌细胞 (VSMCs) 在AAA病变发生过程中起着至关重要的作用.
- 铁亡,一种受调节的细胞死亡途径,与AAA的发展有关.
研究的目的:
- 调查克鲁佩尔样因子5 (KLF5) 在AAA中的VSMCs内调节铁的作用.
- 探索核因子红色素-2-相关因子2/血红素氧酶1 (NRF2/HO-1) 信号通路在KLF5-介导对AAA的影响中的参与.
主要方法:
- 使用 angiotensin II (Ang II) 诱导的AAA小鼠模型和初级VSMCs.
- 通过腺病毒和NRF2抑制剂 (ML385) 给予KLF5过度表达.
- 评估了VSMC和大动脉组织中的铁,炎症,表型切换和沉积.
主要成果:
- 在AAA组织中,KLF5表达减少.
- KLF5过度表达抑制了VSMC铁,炎症和血管化.
- KLF5促进了NRF2的核转移和HO-1上调,产生抗氧化作用.
- 抑制NRF2/HO-1通路部分逆转了KLF5的保护作用.
结论:
- KLF5通过减轻VSMC中的铁和血管化,在AAA中发挥保护作用.
- 在AAA中,NRF2/HO-1信号通路是KLF5保护功能的关键调解者.
- 针对KLF5和NRF2/HO-1通路可能为AAA提供治疗策略.
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