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

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

  • Cell Cycle. 2020 Oct;19(20):2734-2744. doi: 10.1080/15384101.2020.1827183.
Meixia Zhang 1 2 Hechuan Wang 1 Xiaowen Wang 3 Mengjun Bie 3 Kai Lu 1 Hua Xiao 1
Affiliations

Affiliations

  • 1 Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University , Chongqing, China.
  • 2 Institute of Life Science, Chongqing Medical University , Chongqing, China.
  • 3 Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University , Chongqing, China.
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.

Keywords

TGF-β1 signaling pathway; atrial fibrillation; atrial fibrosis; caveolin-1; mitsugumin 53.

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