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双重抑制TGFβ和PDGF改善了RV重塑和功能,以应对RV压力或体积负载

John D Dauz^1,2, Kana Yazaki², Yohei Akazawa²

¹Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.

Physiological reports

|May 5, 2025

概括

用Tranilast (TRN) 双重抑制转化生长因子-β1 (TGFβ1) 和血小板衍生生长因子 (PDGF),改善了右心室 (RV) 的重塑. 针对TGFβ和PDGF通路提供了一种协同方法来缓解RV纤维化和功能障碍.

科学领域:

心血管研究研究心血管研究
纤维化机制纤维化机制
分子信号传输的方法

背景情况:

右心室 (RV) 压力和体积过载导致RV纤维化,功能障碍和死亡,特别是在修复的Fallot四重律中.
转化生长因子-β1 (TGFβ1) 和血小板衍生生长因子 (PDGF) 信号通路与其他器官的纤维化有关,但它们在RV纤维化中的作用尚未完全理解.

研究的目的:

调查PDGF和TGFβ信号在RV纤维化中的作用.
为了确定使用Tranilast (TRN) 的TGFβ和PDGF的双抑制是否可以改善RV重塑,以应对肺动脉带状 (PAB) 或肺吐 (PR).

主要方法:

使用PAB和PR的老鼠模型来诱导RV压力和体积过载.
给药Tranilast (TRN) 评估其对VR纤维化,高和功能的影响.
分析了TGFβ规范信号传递,PDGFRβ表达,ERK1/2活性和下游信号传递通路 (SMAD2/3,JNK,β-catenin).

主要成果:

在PAB大鼠中,TRN降低了TGFβ的规范信号传递,改善了RV纤维化,过度缩小和功能.
在PR模型中,TRN降低了PDGFRβ表达和正常化了ERK1/2活性,从而减少了RV缩和改善了扩张性放松.
通过SMAD2/3,JNK和β-catenin信号传递,确定了PDGF作为RV纤维细胞增殖和激活的驱动因素.

结论:

TGFβ和PDGF信号通路是相互连接的,并且对RV纤维化有显著的贡献.
双重抑制TGFβ和PDGF为改善RV重塑在压力和体积负载条件下提供了一个有希望的协同治疗策略.

关键词:

据PDGF的说法,这是一个很好的方法.在TGFβ中,TGFβ是TGFβ.遗传性心脏病是一种先天性心脏病.有纤维化的纤维化.过度缩的过度缩是一个问题.压力加载的压力加载右心室的右心室.装载量 - 装载量.

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