miR‐141‐5p suppresses vascular smooth muscle cell inflammation, proliferation, and migration via inhibiting the HMGB1/NF‐κB pathway

• Published in: Journal of biochemical and molecular toxicology Vol. 35; no. 8; pp. e22828 - n/a
• Main Authors: Li, Yadong, Li, Haide, Chen, Bin, Yang, Fan, Hao, Zhiying
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc 01.08.2021
• Subjects: Animal models; Apoptosis; Arteriosclerosis; Assaying; Atherosclerosis; Bromodeoxyuridine; Cell migration; Cell proliferation; Chromosome 5; Cytokines; Flow cytometry; HMGB1; HMGB1 protein; Immunomodulation; Inflammation; Low density lipoprotein; miRNA; miR‐141‐5p; Modulators; Molecular modelling; mRNA; Muscles; NF‐κB; Pathogenesis; Polymerase chain reaction; Smooth muscle; vascular smooth muscle cells
• ISSN: 1095-6670; 1099-0461
• DOI: 10.1002/jbt.22828

MicroRNAs (miRNAs) have been identified as significant modulators in the pathogenesis of atherosclerosis (AS). Additionally, the dysregulation of vascular smooth muscle cells (VSMCs) is a crucial biological event during AS. Our study aimed to explore the functional roles and molecular mechanisms of miR‐141‐5p in VSMCs dysfunction. C57BL/6 mice were used to establish AS animal model. Human VSMCs were treated by oxidized low‐density lipoprotein (ox‐LDL) to establish AS cell model. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was employed to probe miR‐141‐5p and high‐mobility group box 1 (HMGB1) mRNA expressions in VSMCs or plasma samples of the mice. Inflammatory cytokines were detected by enzyme‐linked immunosorbent assay kits. Cell counting kit‐8 and bromodeoxyuridine assays were performed to evaluate cell proliferation. Cell migration and apoptosis were detected with Transwell assay and flow cytometry analysis, respectively. The target gene of miR‐141‐5p was predicted with the TargetScan database, and the interaction between miR‐141‐5p and HMGB1/nuclear factor‐κB (NF‐κB) was further validated by dual‐luciferase reporter assay, qRT‐PCR, and Western blot analysis. miR‐141‐5p was found to be decreased in the plasma of patients and mice model with AS. Its expression was also downregulated in VSMCs treated by ox‐LDL. miR‐141‐5p overexpression inhibited the inflammation, proliferation, migration of VSMCs, and promoted the apoptosis of VSMCs. HMGB1 was identified as a direct target of miR‐141‐5p, and miR‐141‐5p could repress the activity of HMGB1/NF‐κB signaling. HMGB1 restoration reversed the effects of miR‐141‐5p, and NF‐κB inhibitor JSH‐23 showed similar effects with miR‐141‐5p mimics. miR‐141‐5p inhibits VSMCs’ dysfunction by targeting the HMGB1/NF‐κB pathway, which probably functions as a protective factor during the development of AS.