MiR-145-5p modulates lipid metabolism and M2 macrophage polarization by targeting PAK7 and regulating β-catenin signaling in hyperlipidemia

• Published in: Canadian journal of physiology and pharmacology 2021-09, Vol.99 (9), p.857-863
• Main Authors: Chen, Huijun, Gao, Jing, Xu, Qian, Wan, Dongmei, Zhai, Wenji, Deng, Limei, Qie, Rui
• Format: Article
• Language: English
• Subjects: Animal models; Animals; beta Catenin - physiology; Bioinformatics; Cardiovascular diseases; Cell activation; Cell Polarity; Cells, Cultured; Cholesterol; Cyclin-dependent kinase inhibitor p21; GTP-binding protein; High cholesterol diet; Humans; Hyperlipidemia; Hyperlipidemias - etiology; Hyperlipidemias - metabolism; hyperlipidémie; Kinases; Lipid Metabolism; Lipids; M2 macrophage polarization; Macrophages; Macrophages - physiology; Male; Metabolism; MicroRNAs - physiology; miR-145-5p; miRNA; mRNA; p21-Activated Kinases - genetics; PAK7; polarisation des macrophages M2; Polarization; Rac1 protein; Rats; Rats, Wistar; Signal Transduction - physiology; voie de signalisation de la β-caténine; β-Catenin; β-catenin signaling
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/cjpp-2020-0539

The present study aims to explore the role of microRNA 145-5p (miR-145-5p) in hyperlipidemia. Using bioinformatics tools and a wide range of function and mechanism assays, we attempted to understand the specific function and potential mechanism of miR-145-5p in hyperlipidemia. A cholesterol-enriched diet induced an increase of serum cholesterol and triacylglycerol but a decrease of serum high-density lipoprotein. MiR-145-5p level was decreased in hyperlipidemia rat models. MiR-145-5p regulated lipid metabolism by antagonizing the alteration of high-density lipoprotein, cholesterol, and triacylglycerol in serum mediated by a cholesterol-enriched diet. In mechanism, miR-145-5p directly bound with p21 protein (RAC1)-activated kinase 7 (PAK7) and negatively regulated mRNA and protein levels of PAK7 in THP-1 cells. Furthermore, miR-145-5p level was negatively associated with PAK7 level in rat cardiac tissues. Finally, overexpression of PAK7 reversed the effects of miR-145-5p on β-catenin activation and M2 macrophages polarization in THP-1 cells. In conclusion, MiR-145-5p modulated lipid metabolism and M2 macrophage polarization by targeting PAK7 and regulating β-catenin signaling in hyperlipidemia, which may provide a potential biomarker for the treatment of hyperlipidemia-induced cardiovascular diseases.