皮洛斯通过ERK1/2 MAPK-依赖的血清反应因子在激活的心脏纤维细胞中调节 lysyl氧化酶
Sruthi Radhakrishnan1, Sachin J Shenoy2, Indraja Devidasan1
1Department of Pathology, Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala, India.
Cell biochemistry and function
|June 1, 2024
概括
皮洛斯调节心脏纤维细胞中的lysyl氧化酶活性,影响心脏损伤后的原交联. 向皮奥斯可以减少心脏硬化,并防止心力衰竭的进展.
科学领域:
- 心血管生物学 心血管生物学
- 矩阵生物学 矩阵生物学
- 纤维化研究 纤维化研究
背景情况:
- 通过lysyl氧化酶交叉连接原蛋白对于心肌损伤后的心脏修复至关重要.
- 过度的交叉连接会使心脏壁硬化,损害左心室功能,导致心力衰竭.
- 矩形细胞蛋白质 (如质蛋白) 在调节这一过程中的作用仍然不清楚.
研究的目的:
- 为了研究皮奥斯在调节心脏纤维细胞中的 lysyl氧化酶 (LOX) 中的作用.
- 阐明涉及到围素介导的LOX调节中的信号通路.
- 评估皮奥斯,LOX和心脏心肌梗塞后心脏重塑之间的体内相关性.
主要方法:
- 用血管素II和TGFβ1.1刺激心脏纤维细胞培养.
- 使用siRNA.RNA进行静素沉默.
- 测量 lysyl氧化酶的活性和表达.
- 对ERK1/2 MAPK和血清响应因子 (SRF) 信号的分析.
- 在体内研究,使用心肌梗塞的老鼠模型.
主要成果:
- 皮洛斯沉默取消了血管激素II和TGFβ1诱导的酸氧化酶上调和活性.
- 皮洛斯激活ERK1/2 MAPK信号导致SRF介导的酸氧化酶表达.
- 在体内,肌痛性心肌梗塞后的纤维性痕组织中,静素和lysyl氧化酶被上调调节.
- 皮奥斯和lysyl氧化酶的升高与左心室壁运动和功能的减少相关.
结论:
- 皮洛斯在心脏纤维细胞中调节 lysyl氧化酶中起着关键的机械作用.
- 环素-ERK1/2 MAPK-SRF通路控制着对损伤的反应中的原交叉连接.
- 皮洛斯是一种潜在的治疗点,可以缓解过度心脏纤维化和心力衰竭的硬化.
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