COMP Improves Ang-II-Induced Atrial Fibrillation via TGF-beta Signaling Pathway

Cartilage oligomeric matrix protein (COMP) regulates transforming growth factor-beta (TGF-beta) 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-beta 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-beta 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-beta 1, 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-beta 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-beta signaling pathway. Thus, our research enriches the understanding of the interaction between COMP and TGF-beta in AF, and provides reference for the pathogenesis and diagnosis of AF.

Automated summary

This study aims to clarify the role of COMP in AF and explore its potential mechanism. A hub gene of AF was identified and verified through bioinformatics and animal experiments. The effect of COMP on AF was examined, and the involvement of the TGF-beta pathway was discussed. The results showed that COMP knockdown could inhibit the activation of the TGF-beta pathway in AF cells, but this phenomenon could be reversed by the activator SRI. COMP acts as a major factor and can improve Ang-II-induced AF via the TGF-beta signaling pathway.