Quercetin improves atrial fibrillation through inhibiting TGF-β/Smads pathway via promoting MiR-135b expression

• Published in: Phytomedicine (Stuttgart) Vol. 93; p. 153774
• Main Authors: Wang, Hongtao, Jiang, Wei, Hu, Yanchao, Wan, Zhaofei, Bai, Hongyuan, Yang, Qiang, Zheng, Qiangsun
• Format: Journal Article
• Language: English
• Published: Elsevier GmbH 01-12-2021
• Subjects: Atrial fibrillation (AF); MiR-135b; Myocardial fibrosis; Quercetin; TGF-β/Smads pathway; Que; TGF-β/Smads pathway; MiR-135b; Myocardial fibrosis; Col1a1; ISO; AF; H&E; Atrial fibrillation (AF); NSR; MUT; CTGF; TGF; OD; Quercetin; RCFs; RT-qPCR
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2021.153774

To investigate the role and mechanism of quercetin in isoprenaline (ISO)-induced atrial fibrillation (AF).
Rat cardiac fibroblasts (RCFs) models and RCFs were used to explore the effect and underlying mechanism of quercetin in isoprenaline (ISO)-induced atrial fibrillation (AF) in vivo and in vitro by a series of experiments.
Differentially expressed microRNAs were screened from human AF tissues using the GEO2R and RT-qPCR. The expressions of TGF-β/Smads pathway molecules (TGFβ1, TGFBR1, Tgfbr1, Tgfbr2, Smad2, Smad3, Smad4) in AF tissues were detected by RT-qPCR and Western blot. The relationships between miR-135b and genes (Tgfbr1, Tgfbr2, Smad2) were analyzed by Pearson correlation, TargetScan and dual-luciferase activity assay. RCFs induced by ISO were treated with quercetin (20 or 50 μM), miR-135b mimic and inhibitor, siTgfbr1 and their corresponding controls, then the cell viability was determined by MTT and the expressions of cyclin D1, α-SMA, collagen-related molecules, TGF-β/Smads pathway molecules, and miR-135b were measured by RT-qPCR and Western blot. ISO-induced rats were treated with quercetin (25 mg/kg/day) via gavage, miR-135b antagomir, agomir and their corresponding controls. The treated rats were used for the detection of miR-135b expression by RT-qPCR, histopathological observation by HE and Masson staining, and the detection of Col1A1 and fibronectin contents by immunohistochemical technique.
The expression of miR-135b was downregulated, and those of TGFBR1, TGFBR2, target genes of miR-135b were upregulated in human AF tissues and negatively regulated by miR-135b in RCFs. Through inhibiting TGF-β/Smads pathway via promoting miR-135b expression, quercetin treatment inhibited proliferation, myofibroblast differentiation and collagen deposition in ISO-treated RCFs, as evidenced by reduced expressions of cyclin D1, α-SMA, collagen-related genes and proteins, and alleviated fibrosis and collagen deposition of atrial tissues in ISO-treated rats.
Quercetin may alleviate AF by inhibiting fibrosis of atrial tissues through inhibiting TGF-β/Smads pathway via promoting miR-135b expression.
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