Ubiquitin proteasome system in cardiac fibrosis

作者：Linqi Zeng, Xiaokai Zhang, Zihang Huang, Shuai Song, Mohan Li, Tongyao Wang, Aijun Sun, Junbo Ge · 发表于：Journal of Advanced Research · 年份：2024 · DOI：10.1016/j.jare.2024.12.006 · 被引用次数：16 · 研究领域：Cardiac Fibrosis and Remodeling、Ubiquitin and proteasome pathways、Cardiovascular Function and Risk Factors

• Reveal that UPS impacts cardiac fibrosis through modulation of the TGF-β signaling pathway as well as TGF-β-independent pathways, including p53, AKT1-p38, and JNK1/2. • Summarize recently studied E3 ligases and DUBs in cardiac fibrosis and their related profibrotic pathways, individually analyzing their roles in this pathological process. • Identify E3s and DUBs with dual roles and explore potential reasons. • Propose that targeting UPS enzymes (especially E3s and DUBs) or using PROTACs and molecular glue to induce target protein degradation is of great promise in the therapy of cardiac fibrosis. Cardiac fibrosis, including reactive fibrosis and replacement fibrosis, is a common pathological process in most cardiovascular diseases. The ubiquitin proteasome system (UPS) plays an important role in the development of fibrosis by mediating the degradation and synthesis of proteins involved in transforming growth factor-β (TGF-β)-dependent and TGF-β-independent fibrous pathways. This review aims to provide an overview of ubiquitinated and deubiquitinated molecules that participating in cardiac fibrosis, with the ultimate purpose to identify promising targets for therapeutic strategies. The UPS primarily impacts cardiac fibrosis through modulation of the TGF-β signaling pathway targeting key molecules involved, including the TGF-β receptors, Smad2/3/4 complexes, and inhibitory Smad7, thereby influencing fibrotic processes. In addition to its effect on TGF-β signaling, UPS also re...