Conclusion
Our findings demonstrated that MSI2 could bind with Fbxo6 to induce Rnaset2 ubiquitination and the activation of chemokine signaling pathway during VSMC phenotypic switch in AS.
Methods
Primary mouse VSMCs were transfected with MSI2 specific siRNA and treated with platelet-derived growth factor-BB (PDGF-BB). The proliferation, cell-cycle, and migration of VSMCs were determined by CCK-8, flow cytometry, wound healing, and transwell assays. Western blot and qRT-PCR were conducted to analyze the protein and mRNA expression. Moreover, the correlation between MSI2, Fbxo6, Rnaset2, and chemokine signaling was predicted and verified using RNAct database, KEGG, wiki, RNA-binding protein immunoprecipitation and co-immunoprecipitation. Moreover, H&E and Oil Red O staining were employed for assessing necrotic core and lipid accumulation in AS mouse aorta tissues. The numbers of B lymphocytes and monocytes, and the levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), and low-density lipoprotein cholesterol (LDL-C) in AS mice blood were investigated using flow cytometry and corresponding commercial kits, respectively.
Objective
The objective of this study is to determine how Musashi-2 (MSI2) affects vascular smooth muscle cell (VSMC) phenotypic switch and contributes to atherosclerosis (AS).
Results
MSI2 was up-regulated in the PDGF-BB-treated VSMCs. Knockdown of MSI2 inhibited VSMC proliferation, cell-cycle, and migration. Moreover, MSI2 regulated VSMC phenotypic switch through binding with Fbxo6 to induce Rnaset2 ubiquitination. MSI2 knockdown inhibited chemokine signaling via regulating Fbxo6/Rnaset2 axis. In AS mice, knockdown of MSI2 inhibited the formation of necrotic core and atherosclerotic plaque, and inhibited chemokine signaling via regulating Fbxo6/Rnaset2 axis.