Department of Cardiovascular Surgery, The Affiliated Hospital of Guangdong Medical University, No. 57, Renmin Avenue South, Xiashan District, Zhangjian City, 524001, Guangdong Province, China.
Department of Cardiovascular and Thoracic Surgery, The Affiliated Hospital of Guangdong Medical University, No. 57, Renmin Avenue South, Xiashan District, Zhangjian City, 524001, Guangdong Province, China.
Cardiovasc Toxicol. 2023 Oct;23(9-10):305-316. doi: 10.1007/s12012-023-09799-1. Epub 2023 Aug 16.
Cartilage oligomeric matrix protein (COMP) regulates transforming growth factor-β (TGF-β) signaling pathway, which has been proved to be associated with skin fibrosis and pulmonary fibrosis. Atrial fibrosis is a major factor of atrial fibrillation (AF). Nevertheless, the interaction between COMP and TGF-β as well as their role in AF remains undefined. The purpose of this study is to clarify the role of COMP in AF and explore its potential mechanism. The hub gene of AF was identified from two datasets using bioinformatics. Furthermore, it was verified by the downregulation of COMP in angiotensin-II (Ang-II)-induced AF in mice. Moreover, the effect on AF was examined using CCK8 assay, ELISA, and western blot. The involvement of TGF-β pathway was further discussed. The expression of COMP was the most significant among all these hub genes. Our experimental results revealed that the protein levels of TGF-β1, phosphorylated Smad2 (P-Smad2), and phosphorylated Smad3 (P-Smad3) were decreased after silencing COMP, which indicated that COMP knockdown could inhibit the activation of TGF-β pathway in AF cells. However, the phenomenon was reversed when the activator SRI was added. COMP acts as a major factor and can improve Ang-II-induced AF via TGF-β signaling pathway. Thus, our research enriches the understanding of the interaction between COMP and TGF-β in AF, and provides reference for the pathogenesis and diagnosis of AF.
软骨寡聚基质蛋白（COMP）调节转化生长因子-β（TGF-β）信号通路，该通路已被证明与皮肤纤维化和肺纤维化有关。心房纤维化是心房颤动（AF）的主要因素。然而，COMP 和 TGF-β 之间的相互作用及其在 AF 中的作用仍未确定。本研究旨在阐明 COMP 在 AF 中的作用，并探讨其潜在机制。使用生物信息学从两个数据集确定了 AF 的枢纽基因。进一步通过下调 Ang-II 诱导的 AF 小鼠中的 COMP 进行了验证。此外，使用 CCK8 测定法、ELISA 和 Western blot 检查了对 AF 的影响。进一步讨论了 TGF-β 途径的参与。在所有这些枢纽基因中，COMP 的表达最为显著。我们的实验结果表明，沉默 COMP 后 TGF-β1、磷酸化 Smad2（P-Smad2）和磷酸化 Smad3（P-Smad3）的蛋白水平降低，这表明 COMP 敲低可抑制 AF 细胞中 TGF-β 通路的激活。然而，当加入激活剂 SRI 时，这种现象被逆转。COMP 作为主要因素，可以通过 TGF-β 信号通路改善 Ang-II 诱导的 AF。因此，我们的研究丰富了 COMP 和 TGF-β 在 AF 中的相互作用的认识，为 AF 的发病机制和诊断提供了参考。
