MicroRNA-21 Negatively Regulates Treg Cells Through a TGF-β1/Smad-Independent Pathway in Patients with Coronary Heart Disease

• 出版年: Cellular Physiology and Biochemistry
• 主要な著者: Sihui Li, Qian Fan, Shaolin He, Tingting Tang, Yuhua Liao, Jiangjiao Xie
• フォーマット: 論文
• 言語: 英語
• 出版事項: Cell Physiol Biochem Press GmbH & Co KG 2015-09-01
• 主題: MiR-21; Treg cells; TGF-β1; Coronary heart disease; Smad7
• オンライン･アクセス: http://www.karger.com/Article/FullText/430214
• ISSN: 1015-8987; 1421-9778

Background: CD4+CD25+FoxP3+ regulatory T cells (Treg cells) play a protective role against the development and progression of the inflammatory disease atherosclerosis (AS). MicroRNA-21 (miR-21) is expressed in Treg cells and is up-regulated in the context of AS and other inflammatory diseases. Aims: This study aimed to determine the role of miR-21 in Treg cell regulation and gene expression during the development of AS in patients with coronary heart disease (CHD). Methods and Results: MiR-21 expression in peripheral blood mononuclear cells (PBMCs) was significantly up-regulated in patients with CHD (acute myocardial infarction (AMI) group, n=24; unstable angina (UA) group, n=21; stable angina (SA) group, n=24) compared with patients with chest pain syndrome (CPS, n=27), and miR-21 expression showed an increasing trend from SA to UA to AMI patients. Moreover, flow cytometry analysis indicated that the frequencies of circulating Treg cells decreased in a manner proportionate opposite with the level of miR-21. Quantitative real-time PCR (qRT-PCR) revealed a decrease in mRNA expression of forkhead box P3 (foxp3), transforming cell growth factor beta 1(TGF-β1) and smad7 (a known target gene of miR-21). ELISA analysis revealed a decrease in TGF-β1 secreted into the plasma. In addition, we transfected PBMCs with a miRNA negative control (NS-m), a miR-21 mimic (miR-21-m), a miRNA inhibitor negative control (NS-i), or a miR-21 inhibitor(miR-21-i). Up-regulation of miR-21 decreased the frequency of circulating Treg cells, decreased the expression levels of foxp3, TGF-β1 and smad7, and decreased the amount of TGF-β1 secreted into the plasma. Consistent with these observations, miR-21 down-regulation increased the frequency of circulating Treg cells, increased the expression of foxp3, TGF-β1 and smad7, and increased the amount of TGF-β1 secreted into the plasma. Conclusions: Because the smad7 expression pattern was similar to that of TGF-β, our study suggests that miR-21 can negatively regulate the frequency of circulating Treg cells through a TGF-β1/smad-independent signaling pathway in PBMCs.