MG53/CAV1 regulates transforming growth factor-β1 signaling-induced atrial fibrosis in atrial fibrillation
| Autor: | Kai Lu, Xiaowen Wang, Meixia Zhang, Hechuan Wang, Mengjun Bie, Hua Xiao |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male 0301 basic medicine Caveolin 1 Down-Regulation Smad2 Protein Biology Rats Sprague-Dawley Transforming Growth Factor beta1 Tripartite Motif Proteins 03 medical and health sciences 0302 clinical medicine Mediator Downregulation and upregulation Fibrosis Atrial Fibrillation medicine Animals Humans Heart Atria Molecular Biology Cells Cultured Cell Proliferation Atrial fibrillation Cell Biology Fibroblasts Middle Aged medicine.disease Rats Up-Regulation 030104 developmental biology Mechanism of action 030220 oncology & carcinogenesis Cancer research Female medicine.symptom Signal transduction Signal Transduction Research Paper Developmental Biology Transforming growth factor |
| Zdroj: | Cell Cycle |
| ISSN: | 1551-4005 1538-4101 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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