MiR-17 Knockdown Promotes Vascular Smooth Muscle Cell Phenotypic Modulation Through Upregulated Interferon Regulator Factor 9 Expression

• Published in: American journal of hypertension 2020-12, Vol.33 (12), p.1119-1126
• Main Authors: Li, Wenyan, Deng, Ping, Wang, Junhua, Li, Zhaofeng, Zhang, Huming
• Format: Article
• Language: English
• ISSN: 0895-7061; 1941-7225
• DOI: 10.1093/ajh/hpaa087

Abstract BACKGROUND MiR-17 is a small noncoding RNA that plays an important role in the development of tumorgenesis, which recently has emerged to be involved in regulation of inflammatory responses and angiogenesis. However, the effect and underlying mechanism of miR-17 on vascular smooth muscle cell (VSMC) phenotypic modulation have not been investigated. METHODS AND RESULTS In the current study, we observed that miR-17 expression tested by real-time polymerase chain reaction (RT-PCR) was downregulated in VSMCs administrated with platelet-derived growth factor-BB stimulation and carotid arteries subjected to wire injury, which were accompanied with decreased VSMC differentiation markers. Loss-of-function strategy demonstrated that miR-17 knockdown promoted VSMC phenotypic modulation characterized as decreased VSMC differentiation marker genes, increased proliferated and migrated capability of VSMC examined by RT-PCR and western blot analysis. Mechanistically, the bioinformatics analysis and luciferase assay demonstrated that miR-17 directly targeted Interferon Regulator Factor 9 (IRF9) and the upregulated IRF9 expression was responsible for the promoted effect miR-17 knockdown on VSMC phenotypic modulation. CONCLUSIONS Taken together, our results demonstrated that miR-17 knockdown accelerated VSMC phenotypic modulation partially through directly targeting to IRF9, which suggested that miR-17 may act as a novel therapeutic target for intimal hyperplasia management.