miR-335-5p regulates the proliferation, migration and phenotypic switching of vascular smooth muscle cells in aortic dissection by directly regulating SP1

Jul 22, 2022Acta biochimica et biophysica Sinica

miR-335-5p controls growth, movement, and type changes of blood vessel muscle cells in aortic dissection by directly regulating SP1

AI simplified

Longevity & Aging on OpenScience ↗PubMed ↗DOI ↗

Abstract

Significant downregulation of miR-335-5p and upregulation of SP1 expression occur in aortic dissection tissues and stimulated vascular smooth muscle cells.

Vascular smooth muscle cells (VSMCs) play a crucial role in the development and progression of aortic dissection.
Loss of miR-335-5p is associated with increased SP1 expression in aortic dissection contexts.
Overexpression of miR-335-5p reduces cell proliferation and migration while enhancing contractile markers in human aortic VSMCs.
SP1 is identified as a target gene regulated by miR-335-5p, with its expression inversely related to miR-335-5p levels in aortic dissection.
Manipulating SP1 levels can reverse the effects of miR-335-5p on VSMC behavior.

AI simplified

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 exploredthrough 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. 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. in vitro in vivo

Full Text

We can’t show the full text here under this license. Use the link below to read it at the source.

View full text (PDF) ↗View full text (HTML) ↗View full text ↗

miR-335-5p regulates the proliferation, migration and phenotypic switching of vascular smooth muscle cells in aortic dissection by directly regulating SP1

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the longevity & aging brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the longevity & aging brief