circ_0004090 Modulates atrial fibrosis through mir-590-5p-mediated regulation of the TGF-β/smad pathway

Atrial fibrosis drives atrial structural remodeling and plays a crucial role in the initiation and maintenance of atrial fibrillation (AF). This study aimed to investigate the underlying mechanism of circ_0004090 in atrial fibrosis.

AngiotensinⅡ (Ang Ⅱ) was used to treat mouse cardiac fibroblasts (MCFs) and C57/B6J mice to establish in vitro and in vivo models of atrial fibrosis. mRNA and protein expression levels were detected using quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) and Western blotting, respectively. CCK-8 assay, EdU proliferation assay, and cell scratch wound healing assay were performed to assess MCFs proliferation and migration. Dual-luciferase reporter assay was employed to validate the interaction between circ_0004090 and miR-590-5p/TGF-β1. Pathological staining was conducted to analyze histopathological changes in mouse atrial tissues.

Expression of circ_0004090 was elevated in the serum of AF patients and in Ang Ⅱ-treated MCFs. Silencing circ_0004090 inhibited the proliferation and migration of Ang Ⅱ-treated fibroblasts and reduced the expression of fibrosis-related genes. Circ_0004090 acted as a molecular sponge to inhibit miR-590-5p expression. Overexpression of miR-590-5p abolished the promoting effects of elevated circ_0004090 on the proliferation, migration, and fibrosis of MCFs. Transforming growth factor-β1 (TGF-β1) was identified as a downstream target of miR-590-5p; circ_0004090 sponged miR-590-5p to regulate TGF-β1 expression. Importantly, experiments in mice confirmed that knockdown of circ_0004090 inhibited atrial fibrosis.

The circ_0004090 downregulates miR-590-5p expression via its molecular sponge function. Reduced miR-590-5p levels lead to derepression of TGF-β1and subsequent activation of the related signaling pathway, thereby promoting Ang Ⅱ-induced atrial fibrosis.