PDF(Pubmed)
Abstract：
Circular RNA (circRNA) has emerged as potential therapeutic targets for cardiovascular diseases. Given the central role of the TGFβ signaling pathway in cardiac remodeling and its potential as a therapeutic target, we hypothesized that a circRNA from this pathway could modulate cardiac remodeling and serve as a heart failure treatment. Therefore, we identified a circRNA, named circSMAD3, that was significantly reduced in murine heart failure models. Functionally, circSMAD3 mitigated cardiomyocyte hypertrophy and inhibited cardiac fibroblast activation in vitro. Mechanistically, circSMAD3 interacts with YBX1, stabilizing it and facilitating its binding to SMAD3 in the nucleus, disrupting the TGFβ/SMAD3 signaling pathway, and ultimately restoring cardiac remodeling. This study highlights circSMAD3 as a promising therapeutic target for heart failure treatment.
摘要：
环状RNA（circularRNA，circRNA）已成为心血管疾病的潜在治疗靶点。鉴于TGFβ信号通路在心脏重塑中的核心作用及其作为治疗靶点的潜力，我们假设来自该通路的circRNA可以调节心脏重塑并作为心力衰竭治疗.因此,我们发现了一个circRNA，命名为circSMAD3，在小鼠心力衰竭模型中显著降低。功能上,circleSMAD3在体外减轻心肌细胞肥大并抑制心脏成纤维细胞活化。机械上,大约SMAD3与YBX1相互作用，使其稳定并促进其与细胞核中的SMAD3结合，破坏TGFβ/SMAD3信号通路，最终恢复心脏重塑.这项研究强调了circSMAD3作为心力衰竭治疗的一个有前途的治疗靶点。
