机构：[1]Department of Biochemistry and Molecular Biology, The Key Laboratory of Neural and Vascular Biology, China Administration of Education, Hebei Medical University,Shijiazhuang 050017, China[2]Department of Central Laboratory, Affiliated Hospital of Hebei University, Baoding 071000, China河北大学附属医院[3]Department of Life Science and GreenDevelopment, Hebei University, Baoding 071000, China[4]Department of Biochemistry and Molecular Biology, Hebei University of Chinese Medicine, Shijiazhuang 050200,China[5]Department of Endocrine, The Second Hospital of Hebei Medical University, Shijiazhuang 050005, China[6]Department of Science and Technology, The SecondHospital of Hebei Medical University, Shijiazhuang 050005, China
Autophagy is associated with the cytoprotection of physiological processes against inflammation and oxidative stress. Salvia miltiorrhiza possesses cardiovascular protective actions and has powerful anti-oxidative and anti-inflammatory effects; however, whether and how Salvia miltiorrhiza-derived microRNAs (miRNAs) protect vascular smooth muscle cells (VSMCs) by inducing autophagy across species are unknown. We first screened and identified Sal-miR-58 from Salvia miltiorrhiza as a natural autophagy inducer. Synthetic Sal-miR-58 suppresses chronic angiotensin II (Ang II) infusion-induced abdominal aortic aneurysm (AAA) formation in mice, as well as induces autophagy in VSMCs and attenuates the inflammatory response elicited by Ang II in vivo and in vitro. Mechanistically, Sal-miR-58 downregulates Kruppel-like factor 3 (KLF3) expression through direct binding to the 30 UTR of KLF3, which in turn relieves KLF3 repression of E3 ubiquitin ligase neural precursor cell-expressed developmentally downregulated 4-like (NEDD4L) expression, whereas NEDD4L upregulation increases the ubiquitination and degradation of the platelet isoform of phosphofructokinase (PFKP), subsequently leading to a decrease in the activation of Akt/mammalian target of rapamycin (mTOR) signaling and facilitating VSMC autophagy induced by Sal-miR-58 in the context of chronic Ang II stimulation and aneurysm formation. Our results provide the first evidence that plant-derived Sal-miR-58 induces autophagy and attenuates inflammation in VSMCs through cross species modulation of the KLF3/NEDD4L/PFKP regulatory pathway.
基金：
National Natural Science Foundation of China [31671182, 31871152, 81770285]; Hebei Scientific Research Project of High-Level Talents [GCC2014026]; Foundation Project of the Affiliated Hospital of Hebei University [2019Q008]; Hebei Scientific Research Project of Traditional Chinese Medicine [2018151, 2018147]
第一作者机构：[1]Department of Biochemistry and Molecular Biology, The Key Laboratory of Neural and Vascular Biology, China Administration of Education, Hebei Medical University,Shijiazhuang 050017, China[2]Department of Central Laboratory, Affiliated Hospital of Hebei University, Baoding 071000, China[3]Department of Life Science and GreenDevelopment, Hebei University, Baoding 071000, China
通讯作者：
通讯机构：[1]Department of Biochemistry and Molecular Biology, The Key Laboratory of Neural and Vascular Biology, China Administration of Education, Hebei Medical University,Shijiazhuang 050017, China[*1]Department of Biochemistry and MolecularBiology, The Key Laboratory of Neural and Vascular Biology, China Administration of Education, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang 050017, China
推荐引用方式(GB/T 7714)：
Qin Yan,Zheng Bin,Yang Gao-shan,et al.Salvia miltiorrhiza-Derived Sal-miR-58 Induces Autophagy and Attenuates Inflammation in Vascular Smooth Muscle Cells[J].MOLECULAR THERAPY-NUCLEIC ACIDS.2020,21:492-511.doi:10.1016/j.omtn.2020.06.015.
医学