MG53/CAV1 regulates transforming growth factor-β1 signaling-induced atrial fibrosis in atrial fibrillation.

Abstract

Atrial fibrosis plays a significant role in the development of atrial fibrillation (AF). Previously, we showed that mitsugumin 53 (MG53) regulates TGF-β1 signaling pathway-induced atrial fibrosis. Recent studies have shown that caveolin-1 (CAV1) is an important anti-fibrosis signaling mediator that inhibits the TGF-β1 signaling pathway. Here, we further study the mechanism underlying the related action of MG53 and CAV1. We demonstrate that CAV1 expression was decreased while MG53 expression was increased in atrial tissue from AF patients. In cultured atrial fibroblasts, MG53 depletion by siRNA caused CAV1 upregulation and TGF-β1/SMAD2 signaling pathway downregulation, while MG53 overexpression via adenovirus had the opposite effect. CAV1 inactivated the TGF-β1/SMAD2 signaling pathway. In addition, using an Ang II-induced fibrosis model, we show that MG53 regulates TGF-β1 signaling via CAV1. Therefore, CAV1 is critical for the MG53 regulation of TGF-β1 signaling pathway-induced atrial fibrosis in AF. These findings reveal the related underlying mechanism of action of MG53 and CAV1 and provide a potential therapeutic target for fibrosis and AF.

• Authors: Meixia Zhang, Hechuan Wang, Xiaowen Wang, Mengjun Bie, Kai Lu, Hua Xiao
• Journal: Cell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 19 Issue 20 Pg. 2734-2744 (10 2020) ISSN: 1551-4005 [Electronic] United States
• PMID: 33000676 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CAV1 protein, human
• Caveolin 1
• Smad2 Protein
• TGFB1 protein, human
• TRIM72 protein, human
• Transforming Growth Factor beta1
• Tripartite Motif Proteins

Topics

• Adult
• Animals
• Atrial Fibrillation (metabolism)
• Caveolin 1 (metabolism)
• Cell Proliferation (physiology)
• Cells, Cultured
• Down-Regulation (physiology)
• Female
• Fibroblasts (metabolism)
• Fibrosis (metabolism)
• Heart Atria (metabolism)
• Humans
• Male
• Middle Aged
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (physiology)
• Smad2 Protein (metabolism)
• Transforming Growth Factor beta1 (metabolism)
• Tripartite Motif Proteins (metabolism)
• Up-Regulation (physiology)