Status and role of the ubiquitin–proteasome system in renal fibrosis
Yizhen Chen, Rong Dai, Meng Cheng, Weili Wang, Chuanjiao Liu, Zeping Cao, Yong Ge, Yiping Wang, Lei Zhang
Abstract
The ubiquitin–proteasome system (UPS) is a basic regulatory mechanism in cells that is essential for maintaining cell homeostasis, stimulating signal transduction, and determining cell fate. These biological processes require coordinated signaling cascades across members of the UPS to achieve substrate ubiquitination and deubiquitination. The role of the UPS in fibrotic diseases has attracted widespread attention, and the aberrant expression of UPS members affects the fibrosis process. In this review, we provide an overview of the UPS and its relevance for fibrotic diseases. Moreover, for the first time, we explore in detail how the UPS promotes or inhibits renal fibrosis by regulating biological processes such as signaling pathways, inflammation, oxidative stress, and the cell cycle, emphasizing the status and role of the UPS in renal fibrosis. Further research on this system may reveal new strategies for preventing renal fibrosis. • The UPS degrades 80–90 % of proteins, which is crucial for cellular processes and homeostasis. • Potential therapeutic targets are identified for renal fibrosis involving E3 ligases and DUBs. • The UPS regulates renal fibrosis via the TGF-β/Smad, Wnt/β-catenin, and PINK1/Parkin pathways. • The UPS influences renal fibrosis through inflammation, oxidative stress, and cell cycle control.