Background
Atrial fibrosis is an important pathophysiological mechanism in the development and maintenance of atrial fibrillation. Trimethylamine N-oxide (TMAO) is one of the most widely studied microbial metabolites involved in the promotion of cardiac fibrosis. TMAO promotes phenotypic transformation, proliferation, and migration and increases collagen secretion in cardiac fibroblasts. The Wnt/β-catenin pathway also plays a key role in the promotion of cardiac fibroblasts into myofibroblasts.
Conclusions
TMAO promotes the transformation of atrial fibroblasts into myofibroblasts by activating Wnt3a/β-catenin signaling pathway.
Methods
The expression of Alpha-smooth muscle actin (α-SMA) was determined to identify the formation of myofibroblasts. The effects of TMAO on the proliferation and migration of atrial fibroblasts were detected by cell counting kit 8, and transwell assays, respectively. Western blot and immunofluorescence were used to detect the activation of the β-catenin pathway by TMAO and the phenotypic transformation and collagen secretion of the atrial fibroblasts. Western blot and immunofluorescence assays were performed to detect the effects of exogenous Wnt3a and TMAO on the activation of β-catenin pathway and the phenotypic transformation of atrial fibroblasts.
Results
TMAO promoted the proliferation and migration of atrial fibroblasts. TMAO also promoted the phenotypic transformation, migration, and collagen secretion of the atrial fibroblasts by activating the β-catenin pathway. Exogenous Wnt3a and TMAO synergistically promoted the activation and phenotypic transformation of the β-catenin pathway in atrial fibroblasts. Conclusions: TMAO promotes the transformation of atrial fibroblasts into myofibroblasts by activating Wnt3a/β-catenin signaling pathway.