MiR-133b as a crucial regulator of TCS-induced cardiotoxicity via activating β-adrenergic receptor signaling pathway in zebrafish embryos.

As a commonly used antibacterial agent in daily consumer products, triclosan (TCS) has attracted significant attention due to its potential environmental risks. In this study, we investigated the toxic effects of TCS exposure (1.4 μM) on heart development in zebrafish embryos. Our findings revealed that TCS exposure caused significant cardiac dysfunction, characterized by pericardial edema, malformations in the heart structure, and a slow heart rate. Additionally, TCS exposure induced oxidative damage and abnormal apoptosis in heart cells through the up-regulation of β-adrenergic receptor (β-AR) signaling pathway genes (adrb1, adrb2a, arrb2b), similar to the effects induced by β-AR agonists. Notably, the adverse effects of TCS exposure were alleviated by β-AR antagonists. Using high-throughput transcriptome miRNA sequencing and targeted miRNA screening, we focused on miR-133b, which targets adrb1 and was down-regulated by TCS exposure, as a potential contributor to TCS-induced cardiotoxicity. Inhibition of miR-133b produced similar toxic effects as TCS exposure, while overexpression of miR-133b down-regulated the β-AR signaling pathway and rescued heart defects caused by TCS. In summary, our findings provide new insights into the mechanisms underlying the cardiotoxic effects of TCS. We suggest that targeting the β-AR pathway and miR-133b may be effective strategies for pharmacotherapy in cardiotoxicity induced by environmental pollutants such as TCS.