通过STAT3 / ATF6 / 自调节PDCD4的下调调节介于MIF诱导的PASMCs的增殖/迁移和血管重塑
Limin Chai1, Qingting Wang1, Yan Wang1
1Department of Respiratory Medicine, The First Affiliated Hospital of Xi'an JiaoTong, University, Xi'an, Shaanxi 710061, People's Republic of China.
European journal of pharmacology
|August 7, 2023
概括
巨细胞迁移抑制因子 (MIF) 通过通过STAT3/ATF6/自途径促进平滑肌肉细胞的增殖,从而导致血管重塑,驱动肺高血压. 准这一轴为肺高血压提供了潜在的治疗策略.
科学领域:
- 心血管生物学 心血管生物学
- 细胞机制 细胞机制
- 分子病理学分子病理学
背景情况:
- 肺高血压 (PH) 涉及肺动脉光滑肌肉细胞 (PASMC) 增殖和血管重塑.
- 在PH中由巨细胞迁移抑制因子 (MIF) 驱动的精确分子通路仍然不完全理解.
研究的目的:
- 阐明MIF诱导PASMC在PH中的增殖,迁移和血管重塑的分子机制.
- 调查信号传感器和转录3 (STAT3) /激活转录因子6 (ATF6) /自/编程细胞死亡因子4 (PDCD4) 轴在MIF介导PH中的作用.
主要方法:
- 使用了初级培养大鼠PASMC和单色素诱导 (MCT) 的大鼠PH模型.
- 研究了MIF对STAT3酸化,ATF6激活,自和PDCD4水平的影响.
- 在干预研究中使用了MIF抑制剂 (4-IPP),ATF6抑制剂 (美拉托尼) 和自抑制剂 ().
主要成果:
- 通过增加STAT3酸化,激活ATF6,触发自,并导致PDCD4降解,MIF促进了PASMC的扩散和迁移.
- 在MCT诱导的PH大鼠的肺组织中观察到MIF,p-STAT3升高,ATF6激活,自增加和PDCD4减少.
- 针对MIF/STAT3/ATF6/自/PDCD4通路的干预措施有效地抑制了PH的PASMC增殖和血管重塑.
结论:
- MIF激活了STAT3/ATF6/自级联,导致PDCD4降解,这驱动了PH的PASMC增殖,迁移和肺血管重塑.
- 在MIF/STAT3/ATF6/自/PDCD4轴代表PH的发展的一个关键途径.
- 准这个轴对治疗肺高血压有潜在的治疗价值.
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