| 1 | miR-335-5p regulates the proliferation,migration and phenotypic switching of vascular smooth muscle cells in aortic dissection by directly regulating SP1显示文摘Uncontrolled proliferation,migration and phenotypic switching of vascular smooth muscle cells(VSMCs)are important steps in the development and progression of aortic dissection(AD).The function and potential mechanism of miR-335-5p in the pathogenesis of AD are explored in this study.Specifically,the biological function of miR-335-5p is explored in vitro through CCK-8,Transwell,immunofluorescence,EdU,wound-healing,RT-qPCR and western blotting assays.In addition,an AD model induced by angiotensin II is used to investigate the function of miR-335-5p in vivo.A dual-luciferase assay is performed to verify the targeting relationship between miR-335-5p and specificity protein 1(SP1).Experiments involving the loss of SP1 function are performed to demonstrate the function of SP1 in the miR-335-5p-mediated regulation of human aortic-VSMCs(HA-VSMCs).AD tissues and platelet-derived growth factor BB(PDGF-BB)-stimulated HA-VSMCs show significant downregulation of miR-335-5p expression and upregulated SP1 expression.Overexpression of miR-335-5p effectively suppresses cell proliferation,migration and synthetic phenotype markers and enhances contractile phenotype markers induced by PDGF-BB treatment.Additionally,SP1 is identified as a target gene downstream of miR-335-5p,and its expression is negatively correlated with miR-335-5p in AD.Upregulation of SP1 partially reverses the inhibitory effect of miR-335-5p on HA-VSMCs,whereas the downregulation of SP1 has the opposite effect.Furthermore,Ad-miR-335-5p clearly suppresses aorta dilatation and vascular media degeneration in the AD model.Our results suggest that miR-335-5p inhibits HA-VSMC proliferation,migration and phenotypic switching by negatively regulating SP1,and indicate that miR-335-5p may be a potential therapeutic target in AD. | Runwei Ma Dayong Zhang Yi Song Jichang Kong Chunjie Mu Pin Shen Wenting Gui | 2022 | Acta Biochimica et Biophysica Sinica2022，54，7： | 0 |
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